📚 Article Archive

A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci.

Jonathan P Bradfield, Hui-Qi Qu, Kai Wang +16 more · 2011 · PLoS genetics · PLOS · added 2026-04-24

Jonathan P Bradfield, Hui-Qi Qu, Kai Wang, Haitao Zhang, Patrick M Sleiman, Cecilia E Kim, Frank D Mentch, Haijun Qiu, Joseph T Glessner, Kelly A Thomas, Edward C Frackelton, Rosetta M Chiavacci, Marcin Imielinski, Dimitri S Monos, Rahul Pandey, Marina Bakay, Struan F A Grant, Constantin Polychronakos, Hakon Hakonarson Show less

Diabetes impacts approximately 200 million people worldwide, of whom approximately 10% are affected by type 1 diabetes (T1D). The application of genome-wide association studies (GWAS) has robustly rev Show more

Diabetes impacts approximately 200 million people worldwide, of whom approximately 10% are affected by type 1 diabetes (T1D). The application of genome-wide association studies (GWAS) has robustly revealed dozens of genetic contributors to the pathogenesis of T1D, with the most recent meta-analysis identifying in excess of 40 loci. To identify additional genetic loci for T1D susceptibility, we examined associations in the largest meta-analysis to date between the disease and ∼2.54 million SNPs in a combined cohort of 9,934 cases and 16,956 controls. Targeted follow-up of 53 SNPs in 1,120 affected trios uncovered three new loci associated with T1D that reached genome-wide significance. The most significantly associated SNP (rs539514, P = 5.66×10⁻¹¹) resides in an intronic region of the LMO7 (LIM domain only 7) gene on 13q22. The second most significantly associated SNP (rs478222, P = 3.50×10⁻⁹ resides in an intronic region of the EFR3B (protein EFR3 homolog B) gene on 2p23; however, the region of linkage disequilibrium is approximately 800 kb and harbors additional multiple genes, including NCOA1, C2orf79, CENPO, ADCY3, DNAJC27, POMC, and DNMT3A. The third most significantly associated SNP (rs924043, P = 8.06×10⁻⁹ lies in an intergenic region on 6q27, where the region of association is approximately 900 kb and harbors multiple genes including WDR27, C6orf120, PHF10, TCTE3, C6orf208, LOC154449, DLL1, FAM120B, PSMB1, TBP, and PCD2. These latest associated regions add to the growing repertoire of gene networks predisposing to T1D. Show less

📄 PDF DOI: 10.1371/journal.pgen.1002293

ADCY3

Axin1 expression facilitates cell death induced by aurora kinase inhibition through PARP activation.

Eun-Jin Choi, Shi-Mun Kim, Ki-Joon Song +2 more · 2011 · Journal of cellular biochemistry · Wiley · added 2026-04-24

Eun-Jin Choi, Shi-Mun Kim, Ki-Joon Song, Jae-Myun Lee, Sun-Ho Kee Show less

Axin, a negative regulator of Wnt signaling, participates in apoptosis, and Axin1 localizes to centrosomes and mitotic spindles, which requires Aurora kinase activity. In this study, Aurora inhibition Show more

Axin, a negative regulator of Wnt signaling, participates in apoptosis, and Axin1 localizes to centrosomes and mitotic spindles, which requires Aurora kinase activity. In this study, Aurora inhibition of Axin1-expressing cells (L-Axin) produced polyploid cells, which died within 48 h posttreatment, whereas Axin2-expressing cells (L-Axin2) survived the same period. These cell death events showed apoptotic signs, such as chromatin condensation and increased sub-G1 populations, as well as cell membrane rupture. Further analysis showed that Aurora kinase inhibitor (AKI) treatment of L-Axin cells induced poly(ADP-ribose) polymerase (PARP) activation, which increased the poly(ADP-ribosyl)ation of cellular proteins and reduced cellular ATP content. PARP inhibition reduced a proportion of dead cells, suggesting PARP involvement in AKI-induced cell death. Also, AKI treatment of L-Axin cells induced mitochondrial apoptosis-inducing factor (AIF) release, but not mitochondrial cytochrome c release or caspase-3 activation. Knockdown of AIF attenuated AKI-induced cell death in L-Axin cells. Thus, our results suggest that Axin1 expression renders L929 cells sensitive to Aurora inhibition-induced cell death in a PARP- and AIF-dependent manner. Show less

no PDF DOI: 10.1002/jcb.23162

AXIN1

DNA synthesis and epigenetic modification during mouse oocyte fertilization by human or hamster sperm injection.

Yong-Nan Xu, Xiang-Shun Cui, Jin-Cheol Tae +2 more · 2011 · Journal of assisted reproduction and genetics · Springer · added 2026-04-24

Yong-Nan Xu, Xiang-Shun Cui, Jin-Cheol Tae, Yong-Xun Jin, Nam-Hyung Kim Show less

To evaluate DNA synthesis and epigenetic modification in mouse oocytes during the first cell cycle following the injection of human or hamster sperm. Mouse oocytes following the injection of human and Show more

To evaluate DNA synthesis and epigenetic modification in mouse oocytes during the first cell cycle following the injection of human or hamster sperm. Mouse oocytes following the injection of human and hamster sperm and cultured in M16 medium. Male and female pronucleus formation, DNA synthesis, histone protein modification, and heterochromatin formation were similar in mouse oocytes injected with human or hamster sperm. However, DNA methylation patterns were altered in mouse oocytes following human sperm injection. Immunocytochemical staining with a histone H3-MeK9 antibody revealed that human and hamster sperm chromatin associated normally with female mouse chromatin, then entered into the metaphase and formed normal, two-cell stage embryos. Although differences in epigenetic modification of DNA were observed, fertilization and cleavage occurred in a species non-specific manner in mouse oocytes. Show less

no PDF DOI: 10.1007/s10815-010-9509-1

CBX1

Protective potential of resveratrol against oxidative stress and apoptosis in Batten disease lymphoblast cells.

Dong-Ho Yoon, Oh-Youn Kwon, Ji Young Mang +5 more · 2011 · Biochemical and biophysical research communications · Elsevier · added 2026-04-24

Dong-Ho Yoon, Oh-Youn Kwon, Ji Young Mang, Myung Jin Jung, Do Yeon Kim, Yoon Kyung Park, Tae-Hwe Heo, Sung-Jo Kim Show less

Batten disease (BD) is the most common form of a group of disorders called neuronal ceroid lipofuscinosis, which are caused by a CLN3 gene mutation. A variety of pathogenic lysosomal storage disorder Show more

Batten disease (BD) is the most common form of a group of disorders called neuronal ceroid lipofuscinosis, which are caused by a CLN3 gene mutation. A variety of pathogenic lysosomal storage disorder mechanisms have been suggested such as oxidative stress, endoplasmic reticulum (ER) stress, and altered protein trafficking. Resveratrol, a stilbenoid found in red grape skin, is a potent antioxidant chemical. Recent studies have suggested that resveratrol may have a curative effect in many neurodegenerative diseases. Therefore, we investigated the activities of resveratrol at the levels of oxidative and ER stress and apoptosis factors using normal and BD lymphoblast cells. We report that the BD lymphoblast cells contained low-levels of superoxide dismutase-1 (SOD-1) due to the long-term stress of reactive oxygen species. However, when we treated the cells with resveratrol, SOD-1 increased to levels observed in normal cells. Furthermore, we investigated the expression of glucose-regulated protein 78 as an ER stress marker. BD cells underwent ER stress, but resveratrol treatment resolved the ER stress in a dose-dependent manner. We further demonstrated that the levels of apoptosis markers such as apoptosis induce factor, cytochrome c, and cleavage of poly (ADP)-ribose polymerase decreased following resveratrol treatment. Thus, we propose that resveratrol may have beneficial effects in patients with BD. Show less

no PDF DOI: 10.1016/j.bbrc.2011.09.019

CLN3

DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells.

Zhiqiang Zhang, Taeil Kim, Musheng Bao +6 more · 2011 · Immunity · Elsevier · added 2026-04-24

Zhiqiang Zhang, Taeil Kim, Musheng Bao, Valeria Facchinetti, Sung Yun Jung, Amir Ali Ghaffari, Jun Qin, Genhong Cheng, Yong-Jun Liu Show less

The innate immune system detects viral infection predominantly by sensing viral nucleic acids. We report the identification of a viral sensor, consisting of RNA helicases DDX1, DDX21, and DHX36, and t Show more

The innate immune system detects viral infection predominantly by sensing viral nucleic acids. We report the identification of a viral sensor, consisting of RNA helicases DDX1, DDX21, and DHX36, and the adaptor molecule TRIF, by isolation and sequencing of poly I:C-binding proteins in myeloid dendritic cells (mDCs). Knockdown of each helicase or TRIF by shRNA blocked the ability of mDCs to mount type I interferon (IFN) and cytokine responses to poly I:C, influenza A virus, and reovirus. Although DDX1 bound poly I:C via its Helicase A domain, DHX36 and DDX21 bound the TIR domain of TRIF via their HA2-DUF and PRK domains, respectively. This sensor was localized within the cytosol, independent of the endosomes. Thus, the DDX1-DDX21-DHX36 complex represents a dsRNA sensor that uses the TRIF pathway to activate type I IFN responses in the cytosol of mDCs. Show less

📄 PDF DOI: 10.1016/j.immuni.2011.03.027

DHX36

Histone deacetylase inhibitor MS-275 stimulates bone formation in part by enhancing Dhx36-mediated TNAP transcription.

Ha-Neui Kim, Jong-Ho Lee, Suk-Chul Bae +4 more · 2011 · Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · Wiley · added 2026-04-24

Ha-Neui Kim, Jong-Ho Lee, Suk-Chul Bae, Hyun-Mo Ryoo, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee Show less

Histone deacetylases (HDACs) deacetylate both histones and nonhistone proteins and play a key role in the regulation of physiologic and aberrant gene expression. Inhibition of HDACs has emerged as a p Show more

Histone deacetylases (HDACs) deacetylate both histones and nonhistone proteins and play a key role in the regulation of physiologic and aberrant gene expression. Inhibition of HDACs has emerged as a promising therapeutic target for cancer and neurologic diseases. In this study we investigated the osteogenic effect and mechanism of action of MS-275, a class I HDAC inhibitor with preference for HDAC1. Both local and systemic administration of MS-275 stimulated bone regeneration in animal models. MS-275 stimulated mRNA expression and activity of the early osteogenic marker tissue-nonspecific alkaline phosphatase (TNAP) in bone tissue and osteogenic cells. By using a series of TNAP promoter deletion constructs and a DNA affinity precipitation assay, we identified DExH-box helicase Dhx36 as a factor that binds to the MS-275 response element in the TNAP promoter. We also found that Dhx36 binding to the MS-275 response element is crucial for MS-275 induction of TNAP transcription. Dhx36 physically interacted with a subset of HDACs (HDAC1 and -4) whose protein levels were downregulated by MS-275, and forced expression of these HDACs blunted the stimulatory effects of MS-275 by a deacetylase activity-independent mechanism(s). Taken together, the results of our study show that MS-275 induces TNAP transcription by decreasing the interaction of HDAC1/4 with Dhx36, which can at least in part contribute to the bone anabolic effects of MS-275. Show less

no PDF DOI: 10.1002/jbmr.426

DHX36

Differential expression of DUSP6 with expression of ERK and Ki-67 in non-small cell lung carcinoma.

Hyunjung Lee, Jin Man Kim, Song-Mei Huang +7 more · 2011 · Pathology, research and practice · Elsevier · added 2026-04-24

Hyunjung Lee, Jin Man Kim, Song-Mei Huang, Seung-Kiel Park, Dong-Hoon Kim, Do Hyung Kim, Choong Sik Lee, Kwang Sun Suh, Eunhee S Yi, Kyung-Hee Kim Show less

Dual specificity phosphatase 6 (DUSP6) is a member of the MAP kinase phophatase family. DUSP6 inactivates extracellular signal-regulated kinase (ERK), belonging to the MAP kinase family, and can act i Show more

Dual specificity phosphatase 6 (DUSP6) is a member of the MAP kinase phophatase family. DUSP6 inactivates extracellular signal-regulated kinase (ERK), belonging to the MAP kinase family, and can act in tumor suppressive pathways. The aim of this study was to investigate associations of DUSP6 expression with expression of ERK and Ki-67 and with clinicopathological parameters in lung adenocarcinoma and squamous cell carcinoma. A total of 102 squamous cell carcinomas and 66 adenocarcinomas were studied using immunohistochemistry for DUSP6, ERK1/2, and Ki-67. In 66 adenocarcinomas, high DUSP6 expression was positively correlated with ERK1/2 expression. High DUSP6 expression was correlated with lower histological grade and lower Ki-67 index in the adenocarcinomas. In 102 squamous cell carcinomas, high DUSP6 expression was correlated with lower ERK expression, with greater smoking pack-years, but not with the Ki-67 index. These results indicate that DUSP6 acts as a negative feedback regulator of ERK in adenocarcinoma progression, but that DUSP6 does not play a role in the downregulation of ERK in squamous cell carcinoma. The differential expression of DUSP6 correlated with Ki-67 index, suggesting that DUSP6 plays an important role in cancer resistance in different subtypes of non-small cell lung carcinoma. Show less

no PDF DOI: 10.1016/j.prp.2011.05.004

DUSP6

Fatty acid desaturase (FADS) gene polymorphisms and insulin resistance in association with serum phospholipid polyunsaturated fatty acid composition in healthy Korean men: cross-sectional study.

Oh Yoen Kim, Hyo Hee Lim, Long In Yang +2 more · 2011 · Nutrition & metabolism · BioMed Central · added 2026-04-24

Oh Yoen Kim, Hyo Hee Lim, Long In Yang, Jey Sook Chae, Jong Ho Lee Show less

We investigated the relationship between fatty acid desaturase (FADS) gene polymorphisms and insulin resistance (IR) in association with serum phospholipid polyunsaturated fatty acid (FA) composition Show more

We investigated the relationship between fatty acid desaturase (FADS) gene polymorphisms and insulin resistance (IR) in association with serum phospholipid polyunsaturated fatty acid (FA) composition in healthy Korean men. Healthy men (n = 576, 30 ~ 79 years old) were genotyped for rs174537 near FADS1 (FEN1-10154G>T), FADS2 (rs174575C>G, rs2727270C>T), and FADS3 (rs1000778C>T) SNPs. Dietary intake, serum phospholipid FA composition and HOMA-IR were measured. Fasting insulin and HOMA-IR were significantly higher in the rs174575G allele carriers than the CC homozygotes, but lower in the rs2727270T allele carriers than the CC homozygotes. The proportion of linoleic acid (18:2ω-6, LA) was higher in the minor allele carriers of FEN1-10154G>T, rs174575C>G and rs2727270C>T than the major homozygotes, respectively. On the other hand, the proportions of dihomo-γ-linolenic acid (20:3ω-6, DGLA) and arachidonic acid (20:4ω-6, AA) in serum phospholipids were significantly lower in the minor allele carriers of FEN1-10154 G>T carriers and rs2727270C>T than the major homozygotes respectively. AA was also significantly lower in the rs1000778T allele carriers than the CC homozygotes. HOMA-IR positively correlated with LA and DGLA and negatively with AA/DGLA in total subjects. Interestingly, rs174575G allele carriers showed remarkably higher HOMA-IR than the CC homozygotes when subjects had higher proportions of DLGA (≥1.412% in total serum phospholipid FA composition) (P for interaction = 0.009) or of AA (≥4.573%) (P for interaction = 0.047). HOMA-IR is associated with FADS gene cluster as well as with FA composition in serum phospholipids. Additionally, HOMA-IR may be modulated by the interaction between rs174575C>G and the proportion of DGLA or AA in serum phospholipids. Show less

📄 PDF DOI: 10.1186/1743-7075-8-24

FADS1

FADS gene polymorphisms in Koreans: association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease.

Jung Hyun Kwak, Jean Kyung Paik, Oh Yoen Kim +4 more · 2011 · Atherosclerosis · Elsevier · added 2026-04-24

Jung Hyun Kwak, Jean Kyung Paik, Oh Yoen Kim, Yangsoo Jang, Sang-Hak Lee, Jose M Ordovas, Jong Ho Lee Show less

We investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans. In this c Show more

We investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans. In this case-control study, CAD patients (n=756, 40-79 years) and healthy controls (n=890) were genotyped for rs174537 near FADS1 (FEN1 rs174537G>T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778). We calculated the odds ratios (ORs) for CAD risk and measured serum PUFA composition and lipid peroxide. Among four SNPs, only rs174537G>T differed in allele frequencies between controls and CAD patients after adjustment for age, BMI, cigarette smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia (P=0.017). The minor T allele was associated with a lower risk of CAD [OR 0.75 (95%CI 0.61-0.92), P=0.006] after adjustment. rs174537T carriers had a significantly higher proportion of linoleic acid (LA, 18:2ω6), lower arachidonic acid (AA, 20:4ω6), and lower ratios of AA/dihomo-γ-linolenic acid (DGLA, 20:3ω6) and AA/LA than G/G subjects in both control and CAD groups. In the control group, 174537T carriers had significantly lower levels of total- and LDL-cholesterol, malondialdehyde, and ox-LDL. In CAD patients, rs174537T carriers showed a larger LDL particle size than G/G subjects. The proportion of AA in serum phospholipids positively correlated with LDL-cholesterol, ox-LDL, and malondialdehyde in controls and with 8-epi-prostaglandin F(2α) in both control and CAD groups. The rs174537T is associated with a lower proportion of AA in serum phospholipids and reduced CAD risk, in association with reduced total- and LDL-cholesterol and lipid peroxides. Show less

no PDF DOI: 10.1016/j.atherosclerosis.2010.10.004

FADS1

Genetic loci associated with lipid concentrations and cardiovascular risk factors in the Korean population.

Mi-Hyun Park, NamHee Kim, Jong-Young Lee +1 more · 2011 · Journal of medical genetics · added 2026-04-24

Mi-Hyun Park, NamHee Kim, Jong-Young Lee, Hyun-Young Park Show less

Dyslipidaemia, a key risk factor for cardiovascular disease (CVD), is strongly influenced by genetic factors. To identify genetic factors affecting blood lipid concentrations and CVD risk factors in t Show more

Dyslipidaemia, a key risk factor for cardiovascular disease (CVD), is strongly influenced by genetic factors. To identify genetic factors affecting blood lipid concentrations and CVD risk factors in the Korean population by a candidate gene association analysis. 21 single nucleotide polymorphisms (SNPs) that have been reported as associated with lipid concentrations in people of European ancestry were selected and their associations with CVD risk factors in Korean populations assessed. Genotype data from 7616 subjects without diabetes or lipid-lowering drugs were obtained from the Korean Association Resource (KARE) project. After adjustment for age and gender, five SNPs were identified that were associated with high-density lipoprotein-cholesterol (HDL-C; rs4420638: p=2.09×10⁻⁷), 11 SNPs with low-density lipoprotein-cholesterol (LDL-C; rs12654264: p=1.29×10⁻⁸) and eight SNPs with triglycerides (TG; rs4420638: p=1.80×10⁻⁶). Through analysis of multiple associations with lipid traits, after adjustment for age, gender, body mass index, smoking, alcohol consumption and hypertension, five SNPs (rs693, rs17321515, rs174547, rs688, rs4420638) were identified that were strongly associated with at least two of the following: HDL-C, LDL-C and TG. Of these, rs693, which lies in the APOB gene, was also significantly associated with the homoeostasis model assessment for insulin resistance (p=6.68×10⁻⁶) and γ-glutamyl transpeptidase (p=2.34×10⁻⁶), and rs174547, which lies in the FADS1 gene and was significantly associated with fasting plasma glucose (p=1.48×10⁻⁶). Several SNPs associated with lipid traits and CVD risk factors were identified. These findings may form the basis for further investigations to identify the causative polymorphisms in dyslipidaemia and CVD. Show less

no PDF DOI: 10.1136/jmg.2010.081000

FADS1

Comparative characterization of GPRC5B and GPRC5CLacZ knockin mice; behavioral abnormalities in GPRC5B-deficient mice.

Takamitsu Sano, Yeon-Jeong Kim, Eriko Oshima +6 more · 2011 · Biochemical and biophysical research communications · Elsevier · added 2026-04-24

Takamitsu Sano, Yeon-Jeong Kim, Eriko Oshima, Chika Shimizu, Hiroshi Kiyonari, Takaya Abe, Hideyoshi Higashi, Kazuyuki Yamada, Yoshio Hirabayashi Show less

Although GPRC5B and GPRC5C are categorized into the G protein-coupled receptor family C, including glutamate receptors, GABA receptors, and taste receptors, their physiological functions remain unknow Show more

Although GPRC5B and GPRC5C are categorized into the G protein-coupled receptor family C, including glutamate receptors, GABA receptors, and taste receptors, their physiological functions remain unknown. Since both receptors are expressed in the brain and evolutionarily conserved from fly to human, it is conceivable that they have significant biological roles particularly in the central nervous system (CNS). We generated GPRC5B- and GPRC5C-deficient mice to examine their roles in the CNS. Both homozygous mice were viable, fertile, and showed no apparent histological abnormalities, though GPRC5B-deficient mice resulted in partial perinatal lethality. We demonstrated that the expressions of GPRC5B and GPRC5C are developmentally regulated and differentially distributed in the brain. GPRC5B-deficient mice exhibited altered spontaneous activity pattern and decreased response to a new environment, while GPRC5C-deficient mice have no apparent behavioral deficits. Thus, GPRC5B has important roles for animal behavior controlled by the CNS. In contrast, GPRC5C does not affect behavior, though it has a high sequence similarity to GPRC5B. These findings suggest that family C, group 5 (GPRC5) receptors in mammals are functionally segregated from their common ancestor. Show less

no PDF DOI: 10.1016/j.bbrc.2011.07.118

GPRC5B

DDR1 receptor tyrosine kinase promotes prosurvival pathway through Notch1 activation.

Hyung-Gu Kim, So-Young Hwang, Stuart A Aaronson +2 more · 2011 · The Journal of biological chemistry · American Society for Biochemistry and Molecular Biology · added 2026-04-24

Hyung-Gu Kim, So-Young Hwang, Stuart A Aaronson, Anna Mandinova, Sam W Lee Show less

DDR1 (discoidin domain receptor tyrosine kinase 1) kinase s highly expressed in a variety of human cancers and occasionally mutated in lung cancer and leukemia. It is now clear that aberrant signaling Show more

DDR1 (discoidin domain receptor tyrosine kinase 1) kinase s highly expressed in a variety of human cancers and occasionally mutated in lung cancer and leukemia. It is now clear that aberrant signaling through the DDR1 receptor is closely associated with various steps of tumorigenesis, although little is known about the molecular mechanism(s) underlying the role of DDR1 in cancer. Besides the role of DDR1 in tumorigenesis, we previously identified DDR1 kinase as a transcriptional target of tumor suppressor p53. DDR1 is functionally activated as determined by its tyrosine phosphorylation, in response to p53-dependent DNA damage. In this study, we report the characterization of the Notch1 protein as an interacting partner of DDR1 receptor, as determined by tandem affinity protein purification. Upon ligand-mediated DDR1 kinase activation, Notch1 was activated, bound to DDR1, and activated canonical Notch1 targets, including Hes1 and Hey2. Moreover, DDR1 ligand (collagen I) treatment significantly increased the active form of Notch1 receptor in the nuclear fraction, whereas DDR1 knockdown cells show little or no increase of the active form of Notch1 in the nuclear fraction, suggesting a novel intracellular mechanism underlying autocrine activation of wild-type Notch signaling through DDR1. DDR1 activation suppressed genotoxic-mediated cell death, whereas Notch1 inhibition by a γ-secretase inhibitor, DAPT, enhanced cell death in response to stress. Moreover, the DDR1 knockdown cancer cells showed the reduced transformed phenotypes in vitro and in vivo xenograft studies. The results suggest that DDR1 exerts prosurvival effect, at least in part, through the functional interaction with Notch1. Show less

no PDF DOI: 10.1074/jbc.M111.236612

HEY2

Generation of functional cardiomyocytes from mouse induced pluripotent stem cells.

Kyoung Ha So, Young Joon Han, Hyo Young Park +8 more · 2011 · International journal of cardiology · Elsevier · added 2026-04-24

Kyoung Ha So, Young Joon Han, Hyo Young Park, Jae Gon Kim, Dong Jun Sung, Young Min Bae, Byoung Chul Yang, Soo Bong Park, Sang Keun Chang, Eun Young Kim, Se Pill Park Show less

Induced pluripotent stem (iPS) cells allow derivation of autologous differentiated cells for cell therapy. The purpose of this study was to compare the cardiac differentiation potential of mouse iPS c Show more

Induced pluripotent stem (iPS) cells allow derivation of autologous differentiated cells for cell therapy. The purpose of this study was to compare the cardiac differentiation potential of mouse iPS cells with embryonic stem (ES) cells and demonstrate that they could produce functional cardiomyocytes. iPS cells were prepared from mouse embryonic fibroblasts by lentiviral mediated expression of four transcription factors (Oct4/Sox2/Klf4/C-myc). To induce cardiac cell differentiation, iPS-S-6 or D3-ES cells were induced to form embryoid bodies (EBs) using a two-medium culture protocol, then plated onto gelatin-coated plates and maintained in DMEM. Following classification of the generation periods of contracting EBs into early (d8-d11), middle (d12-d15) and late (d16-20), iPS cells in the early period exhibited characteristics similar to ES cells. In iPS cells from the middle period group, the ratio of contracting EBs was significantly increased compared to ES cells, and the difference persisted in cells from the late period group (p<0.05). The percentage of contracting EBs formed from iPS and ES cells were 44.8% and 33.3%, respectively. In addition, iPS cell-derived cardiomyocytes exhibited mRNA expression of cardiac mesoderm markers such as GATA4 and NKX2.5, and cardiomyocyte markers such as α1s, α1c, α-MHC, β-MHC, Cx40, TnI, TnT, ANF and Hey2. Single cardiomyocytes exhibited typical cross-striated myofibrillar organization, and electrophysiological studies revealed functional cardiac-specific voltage-gated Na(+), Ca(2+) and K(+) channels. These results demonstrate that functional cardiomyocytes can be generated from iPS cells, and suggest that these cells may be useful for the treatment of cardiovascular disease. Show less

no PDF DOI: 10.1016/j.ijcard.2010.08.052

HEY2

Phenotype restricted genome-wide association study using a gene-centric approach identifies three low-risk neuroblastoma susceptibility Loci.

Le B Nguyen, Sharon J Diskin, Mario Capasso +12 more · 2011 · PLoS genetics · PLOS · added 2026-04-24

Le B Nguyen, Sharon J Diskin, Mario Capasso, Kai Wang, Maura A Diamond, Joseph Glessner, Cecilia Kim, Edward F Attiyeh, Yael P Mosse, Kristina Cole, Achille Iolascon, Marcella Devoto, Hakon Hakonarson, Hongzhe K Li, John M Maris Show less

Neuroblastoma is a malignant neoplasm of the developing sympathetic nervous system that is notable for its phenotypic diversity. High-risk patients typically have widely disseminated disease at diagno Show more

Neuroblastoma is a malignant neoplasm of the developing sympathetic nervous system that is notable for its phenotypic diversity. High-risk patients typically have widely disseminated disease at diagnosis and a poor survival probability, but low-risk patients frequently have localized tumors that are almost always cured with little or no chemotherapy. Our genome-wide association study (GWAS) has identified common variants within FLJ22536, BARD1, and LMO1 as significantly associated with neuroblastoma and more robustly associated with high-risk disease. Here we show that a GWAS focused on low-risk cases identified SNPs within DUSP12 at 1q23.3 (P = 2.07 × 10⁻⁶), DDX4 and IL31RA both at 5q11.2 (P = 2.94 × 10⁻⁶ and 6.54 × 10⁻⁷ respectively), and HSD17B12 at 11p11.2 (P = 4.20 × 10⁻⁷) as being associated with the less aggressive form of the disease. These data demonstrate the importance of robust phenotypic data in GWAS analyses and identify additional susceptibility variants for neuroblastoma. Show less

📄 PDF DOI: 10.1371/journal.pgen.1002026

HSD17B12

Identification of genes concordantly expressed with Atoh1 during inner ear development.

Heejei Yoon, Dong Jin Lee, Myoung Hee Kim +1 more · 2011 · Anatomy & cell biology · added 2026-04-24

Heejei Yoon, Dong Jin Lee, Myoung Hee Kim, Jinwoong Bok Show less

The inner ear is composed of a cochlear duct and five vestibular organs in which mechanosensory hair cells play critical roles in receiving and relaying sound and balance signals to the brain. To iden Show more

The inner ear is composed of a cochlear duct and five vestibular organs in which mechanosensory hair cells play critical roles in receiving and relaying sound and balance signals to the brain. To identify novel genes associated with hair cell differentiation or function, we analyzed an archived gene expression dataset from embryonic mouse inner ear tissues. Since atonal homolog 1a (Atoh1) is a well known factor required for hair cell differentiation, we searched for genes expressed in a similar pattern with Atoh1 during inner ear development. The list from our analysis includes many genes previously reported to be involved in hair cell differentiation such as Myo6, Tecta, Myo7a, Cdh23, Atp6v1b1, and Gfi1. In addition, we identified many other genes that have not been associated with hair cell differentiation, including Tekt2, Spag6, Smpx, Lmod1, Myh7b, Kif9, Ttyh1, Scn11a and Cnga2. We examined expression patterns of some of the newly identified genes using real-time polymerase chain reaction and in situ hybridization. For example, Smpx and Tekt2, which are regulators for cytoskeletal dynamics, were shown specifically expressed in the hair cells, suggesting a possible role in hair cell differentiation or function. Here, by reanalyzing archived genetic profiling data, we identified a list of novel genes possibly involved in hair cell differentiation. Show less

📄 PDF DOI: 10.5115/acb.2011.44.1.69

LMOD1

Integrated expression profiling and genome-wide analysis of ChREBP targets reveals the dual role for ChREBP in glucose-regulated gene expression.

Yun-Seung Jeong, Deokhoon Kim, Yong Seok Lee +13 more · 2011 · PloS one · PLOS · added 2026-04-24

Yun-Seung Jeong, Deokhoon Kim, Yong Seok Lee, Ha-Jung Kim, Jung-Youn Han, Seung-Soon Im, Hansook Kim Chong, Je-Keun Kwon, Yun-Ho Cho, Woo Kyung Kim, Timothy F Osborne, Jay D Horton, Hee-Sook Jun, Yong-Ho Ahn, Sung-Min Ahn, Ji-Young Cha Show less

The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify Show more

The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator. Show less

📄 PDF DOI: 10.1371/journal.pone.0022544

MLXIPL

Dietary ellagic acid attenuates oxidized LDL uptake and stimulates cholesterol efflux in murine macrophages.

Sin-Hye Park, Jung-Lye Kim, Eun-Sook Lee +4 more · 2011 · The Journal of nutrition · added 2026-04-24

Sin-Hye Park, Jung-Lye Kim, Eun-Sook Lee, Seon-Young Han, Ju-Hyun Gong, Min-Kyung Kang, Young-Hee Kang Show less

Foam cell formation is the hallmark of early atherosclerosis. Lipid uptake by scavenger receptors (SR) in macrophages initiates chronic proinflammatory cascades linked to atherosclerosis. It has been Show more

Foam cell formation is the hallmark of early atherosclerosis. Lipid uptake by scavenger receptors (SR) in macrophages initiates chronic proinflammatory cascades linked to atherosclerosis. It has been reported that the upregulation of cholesterol efflux may be protective in the development of atherosclerosis. Ellagic acid, a polyphenolic compound mostly found in berries, walnuts, and pomegranates, possesses antioxidative, growth-inhibiting and apoptosis-promoting activities in cancer cells. However, the antiatherogenic actions of ellagic acid are not well defined. The current study elucidated oxidized LDL handling of ellagic acid in J774A1 murine macrophages. Noncytotoxic ellagic acid suppressed SR-B1 induction and foam cell formation within 6 h after the stimulation of macrophages with oxidized LDL, confirmed by Oil red O staining of macrophages. Ellagic acid at ≤5 μmol/L upregulated PPARγ and ATP binding cassette transporter-1 in lipid-laden macrophages, all responsible for cholesterol efflux. In addition, 5 μmol/L ellagic acid accelerated expression and transcription of the nuclear receptor of liver X receptor-α highly implicated in the PPAR signaling. Furthermore, ellagic acid promoted cholesterol efflux in oxidized LDL-induced foam cells. These results provide new information that ellagic acid downregulated macrophage lipid uptake to block foam cell formation of macrophages and boosted cholesterol efflux in lipid-laden foam cells. Therefore, dietary and pharmacological interventions with berries rich in ellagic acid may be promising treatment strategies to interrupt the development of atherosclerosis. Show less

no PDF DOI: 10.3945/jn.111.144816

NR1H3

Nrf2 inhibits LXRα-dependent hepatic lipogenesis by competing with FXR for acetylase binding.

Hee Yeon Kay, Won Dong Kim, Se Jin Hwang +4 more · 2011 · Antioxidants & redox signaling · added 2026-04-24

Hee Yeon Kay, Won Dong Kim, Se Jin Hwang, Hueng-Sik Choi, Richard K Gilroy, Yu-Jui Yvonne Wan, Sang Geon Kim Show less

The nuclear receptor liver X receptor-α (LXRα) stimulates lipogenesis, leading to steatosis. Nuclear factor erythroid-2-related factor-2 (Nrf2) contributes to cellular defense mechanism by upregulatin Show more

The nuclear receptor liver X receptor-α (LXRα) stimulates lipogenesis, leading to steatosis. Nuclear factor erythroid-2-related factor-2 (Nrf2) contributes to cellular defense mechanism by upregulating antioxidant genes, and may protect the liver from injury inflicted by fat accumulation. However, whether Nrf2 affects LXRα activity is unknown. This study investigated the inhibitory role of Nrf2 in hepatic LXRα activity and the molecular basis. A deficiency of Nrf2 enhanced the ability of LXRα agonist to promote hepatic steatosis, as mediated by lipogenic gene induction. In hepatocytes, Nrf2 overexpression repressed gene transactivation by LXR-binding site activation. Consistently, treatment of mice with sulforaphane (an Nrf2 activator) suppressed T0901317-induced lipogenesis, as confirmed by the experiments using hepatocytes. Nrf2 activation promoted deacetylation of farnesoid X receptor (FXR) by competing for p300, leading to FXR-dependent induction of small heterodimer partner (SHP), which was responsible for the repression of LXRα-dependent gene transcription. In human steatotic samples, the transcript levels of LXRα and SREBP-1 inversely correlated with those of Nrf2, FXR, and SHP. Our findings offer the mechanism to explain how decrease in Nrf2 activity in hepatic steatosis could contribute to the progression of NAFLD, providing the use of Nrf2 as a molecular biomarker to diagnose NAFLD. As certain antioxidants have the abilities to activate Nrf2, clinicians might utilize the activators of Nrf2 as a new therapeutic approach to prevent and/or treat NAFLD. Nrf2 activation inhibits LXRα activity and LXRα-dependent liver steatosis by competing with FXR for p300, causing FXR activation and FXR-mediated SHP induction. Our findings provide important information on a strategy to prevent and/or treat steatosis. Show less

no PDF DOI: 10.1089/ars.2010.3834

NR1H3

Oxygenated derivatives of cholesterol promote hepatitis B virus gene expression through nuclear receptor LXRα activation.

Hye Young Kim, Hyun Kook Cho, Hyeong Hoe Kim +1 more · 2011 · Virus research · Elsevier · added 2026-04-24

Hye Young Kim, Hyun Kook Cho, Hyeong Hoe Kim, Jaehun Cheong Show less

Hepatitis B virus (HBV) gene expression and replication are regulated by the activation of a number of liver-enriched transcription factors dependent on intracellular and extracellular stimuli. Howeve Show more

Hepatitis B virus (HBV) gene expression and replication are regulated by the activation of a number of liver-enriched transcription factors dependent on intracellular and extracellular stimuli. However, the association between the metabolic events and HBV gene expression remains unclear. In this study, we assessed the effects of cholesterol metabolism on HBV viral replication and gene expression. Exposure of oxygenated derivatives of cholesterol (oxysterols) increased HBV gene expression and viral promoter activity. This increase in HBV transcription and replication was directed by nuclear receptor LXRα induction in the presence of oxysterols. In addition, HBV viral expression by oxysterol was inhibited through small heterodimer partner and sterol regulatory element-binding protein 2, key regulators of cholesterol synthesis. When IFNα and oxysterols were co-incubated, oxysterols and LXRα significantly reduced the anti-HBV effects of IFNα. These results point to a novel mechanism of oxysterol-mediated gene regulation in HBV replication and a potent mechanism underlying the failure of IFNα-based treatment. Show less

no PDF DOI: 10.1016/j.virusres.2011.03.010

NR1H3

Inhibition of LXRα-dependent steatosis and oxidative injury by liquiritigenin, a licorice flavonoid, as mediated with Nrf2 activation.

Young Woo Kim, Young Mi Kim, Yoon Mee Yang +5 more · 2011 · Antioxidants & redox signaling · added 2026-04-24

Young Woo Kim, Young Mi Kim, Yoon Mee Yang, Hee Yeon Kay, Won Dong Kim, Jee Woo Lee, Se Jin Hwang, Sang Geon Kim Show less

Liver X receptor-α (LXRα) functions as a major regulator of lipid homeostasis through activation of sterol regulatory element binding protein-1c (SREBP-1c), which promotes hepatic steatosis and steato Show more

Liver X receptor-α (LXRα) functions as a major regulator of lipid homeostasis through activation of sterol regulatory element binding protein-1c (SREBP-1c), which promotes hepatic steatosis and steatohepatitis. NF-E2-related factor 2 (Nrf2) is the crucial transcription factor that is necessary for the induction of antioxidant enzymes. This study investigated the potential of liquiritigenin (LQ), a hepatoprotective flavonoid in licorice, to inhibit LXRα-induced hepatic steatosis, and the underlying mechanism of the action. LQ treatment attenuated fat accumulation and lipogenic gene induction in the liver of mice fed a high fat diet. Also, LQ had the ability to inhibit oxidative liver injury, as shown by decreases in thiobarbituric acid reactive substances formation and nitrotyrosinylation. Moreover, LQ treatment antagonized LXRα agonist (T0901317)-mediated SREBP-1c activation, and transactivation of the lipogenic target genes. LQ was found to activate Nrf2, and the ability of LQ to inhibit LXRα-mediated SREBP-1c activation was reversed by Nrf2 deficiency, which supports the inhibitory role of Nrf2 in LXRα-dependent lipogenesis. Consistently, treatment with other Nrf2 activators or forced expression of Nrf2 also inhibited LXRα-mediated SREBP-1c activation. Our results demonstrate that LQ has an efficacy to activate Nrf2, which contributes to inhibiting the activity of LXRα that leads to SREBP-1c induction and hepatic steatosis. Show less

no PDF DOI: 10.1089/ars.2010.3260

NR1H3

Role of BMI-associated loci identified in GWAS meta-analyses in the context of common childhood obesity in European Americans.

Jianhua Zhao, Jonathan P Bradfield, Haitao Zhang +11 more · 2011 · Obesity (Silver Spring, Md.) · Nature · added 2026-04-24

Jianhua Zhao, Jonathan P Bradfield, Haitao Zhang, Patrick M Sleiman, Cecilia E Kim, Joseph T Glessner, Sandra Deliard, Kelly A Thomas, Edward C Frackelton, Mingyao Li, Rosetta M Chiavacci, Robert I Berkowitz, Hakon Hakonarson, Struan F A Grant Show less

Obesity is a serious health concern for children and adolescents, particularly in Western societies, where its incidence is now considered to have reached epidemic proportions. A number of genetic det Show more

Obesity is a serious health concern for children and adolescents, particularly in Western societies, where its incidence is now considered to have reached epidemic proportions. A number of genetic determinants of adult BMI have already been established through genome wide association studies (GWAS), most recently from the GIANT meta-analysis of such datasets combined. In this current study of European Americans, we examined the 32 loci detected in that GIANT study in the context of common childhood obesity within a cohort of 1,097 cases (defined as BMI ≥95th percentile), together with 2,760 lean controls (defined as BMI <50th percentile), aged between 2 and 18 years old. Nine of these single-nucleotide polymorphims (SNPs) yielded at least nominal evidence for association with common childhood obesity, namely at the FTO, TMEM18, NRXN3, MC4R, SEC16B, GNPDA2, TNNI3K, QPCTL, and BDNF loci. However, overall 28 of the 32 loci showed directionally consistent effects to that of the adult BMI meta-analysis. We conclude that among the 32 loci that have been reported to associate with adult BMI in the largest meta-analysis of BMI to date, at least nine also contribute to the determination of common obesity in childhood in European Americans, as demonstrated by their associations in our pediatric cohort. Show less

no PDF DOI: 10.1038/oby.2011.237

NRXN3

Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25.

Yukio Nakamura, Koji Yamamoto, Xinjun He +13 more · 2011 · Nature communications · Nature · added 2026-04-24

Yukio Nakamura, Koji Yamamoto, Xinjun He, Bungo Otsuki, Youngwoo Kim, Hiroki Murao, Tsunemitsu Soeda, Noriyuki Tsumaki, Jian Min Deng, Zhaoping Zhang, Richard R Behringer, Benoit de Crombrugghe, John H Postlethwait, Matthew L Warman, Takashi Nakamura, Haruhiko Akiyama Show less

Sox9 is a direct transcriptional activator of cartilage-specific extracellular matrix genes and has essential roles in chondrogenesis. Mutations in or around the SOX9 gene cause campomelic dysplasia o Show more

Sox9 is a direct transcriptional activator of cartilage-specific extracellular matrix genes and has essential roles in chondrogenesis. Mutations in or around the SOX9 gene cause campomelic dysplasia or Pierre Robin Sequence. However, Sox9-dependent transcriptional control in chondrogenesis remains largely unknown. Here we identify Wwp2 as a direct target of Sox9. Wwp2 interacts physically with Sox9 and is associated with Sox9 transcriptional activity via its nuclear translocation. A yeast two-hybrid screen using a cDNA library reveals that Wwp2 interacts with Med25, a component of the Mediator complex. The positive regulation of Sox9 transcriptional activity by Wwp2 is mediated by the binding between Sox9 and Med25. In zebrafish, morpholino-mediated knockdown of either wwp2 or med25 induces palatal malformation, which is comparable to that in sox9 mutants. These results provide evidence that the regulatory interaction between Sox9, Wwp2 and Med25 defines the Sox9 transcriptional mechanisms of chondrogenesis in the forming palate. Show less

no PDF DOI: 10.1038/ncomms1242

WWP2

Tyr1 and Ile7 of glucose-dependent insulinotropic polypeptide (GIP) confer differential ligand selectivity toward GIP and glucagon-like peptide-1 receptors.

Mi Jin Moon, Hee Young Kim, Sin Gon Kim +4 more · 2010 · Molecules and cells · Springer · added 2026-04-24

Mi Jin Moon, Hee Young Kim, Sin Gon Kim, Juri Park, Dong Seop Choi, Jong-Ik Hwang, Jae Young Seong Show less

Glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones released in response to food intake and potentiate insulin secretion from pancreatic beta c Show more

Glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones released in response to food intake and potentiate insulin secretion from pancreatic beta cells through their distinct yet related G protein-coupled receptors, GLP1R and GIPR. While GLP-1 and GIP exhibit similarity in their N-terminal sequence and overall alpha-helical structure, GLP-1 does not bind to GIPR and vice versa. To determine which amino acid residues of these peptide ligands are responsible for specific interaction with their respective receptors, we generated mutant GIP in which several GLP-1-specific amino acid residues were substituted for the original amino acids. The potency of the mutant ligands was examined using HEK293 cells transfected with GLP1R or GIPR expression plasmids together with a cAMP-responsive element-driven luciferase (CRE-luc) reporter plasmid. A mutated GIP peptide in which Tyr(1), Ile(7), Asp(15), and His(18) were replaced by His, Thr, Glu, and Ala, respectively, was able to activate both GLP1R and GIPR with moderate potency. Replacing the original Tyr(1) and/or Ile(7) in the N-terminal moiety of this mutant peptide allowed full activation of GIPR but not of GLP1R. However, reintroducing Asp(15) and/or His(18) in the central alpha-helical region did not significantly alter the ligand potency. These results suggest that Tyr/His(1) and Ile/Thr(7) of GIP/GLP-1 peptides confer differential ligand selectivity toward GIPR and GLP1R. Show less

no PDF DOI: 10.1007/s10059-010-0100-5

GIPR

Interactions between the APOA5 -1131T>C and the FEN1 10154G>T polymorphisms on ω6 polyunsaturated fatty acids in serum phospholipids and coronary artery disease.

Ju Yeon Park, Jean Kyung Paik, Oh Yoen Kim +3 more · 2010 · Journal of lipid research · added 2026-04-24

Ju Yeon Park, Jean Kyung Paik, Oh Yoen Kim, Jey Sook Chae, Yangsoo Jang, Jong Ho Lee Show less

We determined the contribution of the combination of FEN1 10154G>T with the most significant association in the analysis of plasma arachidonic acid (AA, 20:4ω6) and the APOA5-1131T>C on phospholipid ω Show more

We determined the contribution of the combination of FEN1 10154G>T with the most significant association in the analysis of plasma arachidonic acid (AA, 20:4ω6) and the APOA5-1131T>C on phospholipid ω6PUFA and coronary artery disease (CAD). Patients with CAD (n = 807, 27-81 years of age) and healthy controls (n = 1123) were genotyped for FEN1 10154G>T and APOA5-1131T>C. We found a significant interaction between these two genes for CAD risk (P = 0.007) adjusted for confounding factors. APOA5-1131C allele carriers had a higher CAD risk [odds ratio (OR):1.484, 95% confidence interval (CI):1.31-1.96; P = 0.005] compared with APOA5-1131TT individuals in the FEN1 10154GG genotype group but not in the FEN1 10154T allele group (OR:1.096, 95%CI:0.84-1.43; P = 0.504). Significant interactions between these two genes were also observed for the AA proportion (P = 0.04) and the ratio of AA/linoleic acid (LA, 18:2ω6) (P = 0.004) in serum phospholipids of controls. The APOA5-1131C allele was associated with lower AA (P = 0.027) and AA/LA (P = 0.014) only in controls carrying the FEN1 10154T allele. In conclusion, the interaction between these genes suggests that the FEN1 10154T variant allele decreases AA and AA/LA in the serum phospholipids of carriers of the APOA5-1131C allele, but contributes no significant increase in CAD risk for this population subset despite their increased triglylcerides and decreased apoA5. Show less

no PDF DOI: 10.1194/jlr.M010330

APOA5

APOA5-1131T>C genotype effects on apolipoprotein A5 and triglyceride levels in response to dietary intervention and regular exercise (DIRE) in hypertriglyceridemic subjects.

Yangsoo Jang, Jey Sook Chae, Oh Yoen Kim +5 more · 2010 · Atherosclerosis · Elsevier · added 2026-04-24

Yangsoo Jang, Jey Sook Chae, Oh Yoen Kim, Hey Jun Park, Ji Young Kim, Jean Kyung Paik, Sang-Hyun Lee, Jong Ho Lee Show less

We aimed to determine the influence of apolipoprotein A5 gene (APOA5)-1131T>C single nucleotide polymorphism on the effects of dietary intervention and regular exercise (DIRE) targeting ApoA5 and trig Show more

We aimed to determine the influence of apolipoprotein A5 gene (APOA5)-1131T>C single nucleotide polymorphism on the effects of dietary intervention and regular exercise (DIRE) targeting ApoA5 and triglyceride (TG) concentrations. Hypertriglyceridemia patients (TG, 150-500mg/dL, n=283) undertook a 12-week DIRE (replacing 1/3 of refined rice in their diets with legumes, increasing vegetable intake, and regular walking). Pre-treatment, no genotype-related differences were detected in ApoA5, TG, or HDL cholesterol levels; however, post-treatment, subjects homozygous (T/T) for the T allele had lower serum TG (P=0.009) and higher HDL cholesterol (P=0.036) than other subjects. In T/T subjects, after adjustments for age, sex and weight changes (r1) or initial TG levels (r2), changes in ApoA5 levels negatively correlated with TG changes (r1=-0.29, P=0.05, r2=-0.28, P<0.1) and positively correlated with changes in HDL cholesterol (r1=0.30, P<0.05, r2=0.32, P<0.05) and free fatty acid (r1=0.38, P<0.01, r2=0.40, P<0.01). In those with moderate hypertriglyceridemia (TG, 200-500mg/dL, n=130), APOA5-1131T/T carriers achieved significantly lower TG (P=0.007) and higher HDL cholesterol (P<0.001) than -1131C allele carriers. Additionally, statistically significant interactions between the -1131T>C and the compliance of DIRE were found for the change in TG (P=0.002) and HDL cholesterol (P=0.039). In good compliance group, T/T subjects showed greater reduction of TG and higher increase of HDL cholesterol than other subjects. On the other hand, non-good compliance group had no significant improvement in these variables. APOA5-1131T/T carriers may benefit more from the DIRE than C allele carriers. These effects were remarkable in patients with moderate hypertriglyceridemia and the individuals with good compliance. Show less

no PDF DOI: 10.1016/j.atherosclerosis.2010.03.014

APOA5

Contribution of APOA5-1131C allele to the increased susceptibility of diabetes mellitus in association with higher triglyceride in Korean women.

Ki Ho Lee, Oh Yoen Kim, Hyo Hee Lim +3 more · 2010 · Metabolism: clinical and experimental · Elsevier · added 2026-04-24

Ki Ho Lee, Oh Yoen Kim, Hyo Hee Lim, Young Jin Lee, Yangsoo Jang, Jong Ho Lee Show less

Apolipoprotein A5 (APOA5) -1131C allele is associated with higher triglyceride, an independent cardiovascular risk factor and a commonly recognized lipid abnormality in diabetes mellitus (DM). We inve Show more

Apolipoprotein A5 (APOA5) -1131C allele is associated with higher triglyceride, an independent cardiovascular risk factor and a commonly recognized lipid abnormality in diabetes mellitus (DM). We investigated the association of APOA5 -1131T>C or S19W with DM. Study subjects were all women and categorized into metabolically healthy controls (n = 2033) and DM subjects (n = 304). Association of APOA5 -1131T>C with DM was calculated by odds ratio (OR). Anthropometric parameters, fasting glucose, and lipid profiles were measured. C carriers, particularly those with CC homozygote, had higher triglyceride and lower high-density lipoprotein cholesterol in both healthy controls (P < .001 and P < .001) and DM patients (P = .002 and P = .006) after the adjustment for age, body mass index, menopause, smoking, and drinking. APOA5 -1131C allele was associated with an increased risk of DM (OR, 1.61 [95% confidence interval {CI}, 1.23-2.10]; P < .001) after adjustment for the above confounders. Further adjustment for fasting triglyceride or/and high-density lipoprotein cholesterol attenuated a little bit, but still significantly increased the risk of DM in C carriers (OR(2), 1.36 [95% CI, 1.02-1.80]; P = .035 and OR(3), 1.36 [95% CI, 1.032-1.79]; P = .029, respectively). Interestingly, C allele carriers in DM patients showed a positive correlation between fasting glucose and triglyceride after the adjustment (r = 0.172, P = .035). On the other hand, this significant correlation was not observed in healthy women. Regarding S19W, minor allele was not found in our study population from prescreening test. In conclusion, APOA5 -1131C allele may contribute to the increased susceptibility of DM in Korean women. In addition, positive correlation between fasting glucose and triglyceride in C carriers of DM patients suggested that C allele in hyperglycemic states may be more susceptible to the risk of cardiovascular disease. Show less

no PDF DOI: 10.1016/j.metabol.2010.02.008

APOA5

Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α.

Curtis A Thorne, Alison J Hanson, Judsen Schneider +16 more · 2010 · Nature chemical biology · Nature · added 2026-04-24

Curtis A Thorne, Alison J Hanson, Judsen Schneider, Emilios Tahinci, Darren Orton, Christopher S Cselenyi, Kristin K Jernigan, Kelly C Meyers, Brian I Hang, Alex G Waterson, Kwangho Kim, Bruce Melancon, Victor P Ghidu, Gary A Sulikowski, Bonnie LaFleur, Adrian Salic, Laura A Lee, David M Miller, Ethan Lee Show less

Wnt/β-catenin signaling is critically involved in metazoan development, stem cell maintenance and human disease. Using Xenopus laevis egg extract to screen for compounds that both stabilize Axin and p Show more

Wnt/β-catenin signaling is critically involved in metazoan development, stem cell maintenance and human disease. Using Xenopus laevis egg extract to screen for compounds that both stabilize Axin and promote β-catenin turnover, we identified an FDA-approved drug, pyrvinium, as a potent inhibitor of Wnt signaling (EC(50) of ∼10 nM). We show pyrvinium binds all casein kinase 1 (CK1) family members in vitro at low nanomolar concentrations and pyrvinium selectively potentiates casein kinase 1α (CK1α) kinase activity. CK1α knockdown abrogates the effects of pyrvinium on the Wnt pathway. In addition to its effects on Axin and β-catenin levels, pyrvinium promotes degradation of Pygopus, a Wnt transcriptional component. Pyrvinium treatment of colon cancer cells with mutation of the gene for adenomatous polyposis coli (APC) or β-catenin inhibits both Wnt signaling and proliferation. Our findings reveal allosteric activation of CK1α as an effective mechanism to inhibit Wnt signaling and highlight a new strategy for targeted therapeutics directed against the Wnt pathway. Show less

📄 PDF DOI: 10.1038/nchembio.453

AXIN1

Genome wide association (GWA) predictors of anti-TNFalpha therapeutic responsiveness in pediatric inflammatory bowel disease.

Marla C Dubinsky, Ling Mei, Madison Friedman +9 more · 2010 · Inflammatory bowel diseases · Wiley · added 2026-04-24

Marla C Dubinsky, Ling Mei, Madison Friedman, Tanvi Dhere, Talin Haritunians, Hakon Hakonarson, Cecilia Kim, Joseph Glessner, Stephan R Targan, Dermot P McGovern, Kent D Taylor, Jerome I Rotter Show less

Interindividual variation in response to anti-TNFalpha therapy may be explained by genetic variability in disease pathogenesis or mechanism of action. Recent genome-wide association studies (GWAS) in Show more

Interindividual variation in response to anti-TNFalpha therapy may be explained by genetic variability in disease pathogenesis or mechanism of action. Recent genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) have increased our understanding of the genetic susceptibility to IBD. The aim was to test associations of known IBD susceptibility loci and novel "pharmacogenetic" GWAS identified loci with primary nonresponse to anti-TNFalpha in pediatric IBD patients and develop a predictive model of primary nonresponse. Primary nonresponse was defined using the Harvey Bradshaw Index (HBI) for Crohn's disease (CD) and partial Mayo score for ulcerative colitis (UC). Genotyping was performed using the Illumina Infinium platform. Chi-square analysis tested associations of phenotype and genotype with primary nonresponse. Genetic associations were identified by testing known IBD susceptibility loci and by performing a GWAS for primary nonresponse. Stepwise multiple logistic regression was performed to build predictive models. Nonresponse occurred in 22 of 94 subjects. Six known susceptibility loci were associated with primary nonresponse (P < 0.05). Only the 21q22.2/BRWDI loci remained significant in the predictive model. The most predictive model included 3 novel "pharmacogenetic" GWAS loci, the previously identified BRWD1, pANCA, and a UC diagnosis (R(2) = 0.82 and area under the curve [AUC] = 0.98%). The relative risk of nonresponse increased 15-fold when number of risk factors increased from 0-2 to > or =3. The combination of phenotype and genotype is most predictive of primary nonresponse to anti-TNFalpha in pediatric IBD. Defining predictors of response to anti-TNFalpha may allow the identification of patients who will not benefit from this class of therapy. Show less

📄 PDF DOI: 10.1002/ibd.21174

BRWD1

Aspartate-glutamate-alanine-histidine box motif (DEAH)/RNA helicase A helicases sense microbial DNA in human plasmacytoid dendritic cells.

Taeil Kim, Shwetha Pazhoor, Musheng Bao +8 more · 2010 · Proceedings of the National Academy of Sciences of the United States of America · National Academy of Sciences · added 2026-04-24

Taeil Kim, Shwetha Pazhoor, Musheng Bao, Zhiqiang Zhang, Shino Hanabuchi, Valeria Facchinetti, Laura Bover, Joel Plumas, Laurence Chaperot, Jun Qin, Yong-Jun Liu Show less

Toll-like receptor 9 (TLR9) senses microbial DNA and triggers type I IFN responses in plasmacytoid dendritic cells (pDCs). Previous studies suggest the presence of myeloid differentiation primary resp Show more

Toll-like receptor 9 (TLR9) senses microbial DNA and triggers type I IFN responses in plasmacytoid dendritic cells (pDCs). Previous studies suggest the presence of myeloid differentiation primary response gene 88 (MyD88)-dependent DNA sensors other than TLR9 in pDCs. Using MS, we investigated C-phosphate-G (CpG)-binding proteins from human pDCs, pDC-cell lines, and interferon regulatory factor 7 (IRF7)-expressing B-cell lines. CpG-A selectively bound the aspartate-glutamate-any amino acid-aspartate/histidine (DExD/H)-box helicase 36 (DHX36), whereas CpG-B selectively bound DExD/H-box helicase 9 (DHX9). Although the aspartate-glutamate-alanine-histidine box motif (DEAH) domain of DHX36 was essential for CpG-A binding, the domain of unknown function 1605 (DUF1605 domain) of DHX9 was required for CpG-B binding. DHX36 is associated with IFN-alpha production and IRF7 nuclear translocation in response to CpG-A, but DHX9 is important for TNF-alpha and IL-6 production and NF-kappaB activation in response to CpG-B. Knocking down DHX9 or DHX36 significantly reduced the cytokine responses of pDCs to a DNA virus but had no effect on the cytokine responses to an RNA virus. We further showed that both DHX9 and DHX36 are localized within the cytosol and are directly bound to the Toll-interleukin receptor domain of MyD88 via their helicase-associated domain 2 and DUF domains. This study demonstrates that DHX9/DHX36 represent the MyD88-dependent DNA sensors in the cytosol of pDCs and suggests a much broader role for DHX helicases in viral sensing. Show less

no PDF DOI: 10.1073/pnas.1006539107

DHX36

Identification of 15 loci influencing height in a Korean population.

Jae-Jung Kim, Hae-In Lee, Taesung Park +9 more · 2010 · Journal of human genetics · Nature · added 2026-04-24

Jae-Jung Kim, Hae-In Lee, Taesung Park, Kyunga Kim, Jong-Eun Lee, Nam Han Cho, Chol Shin, Yoon Shin Cho, Jong-Young Lee, Bok-Ghee Han, Han-Wook Yoo, Jong-Keuk Lee Show less

Height is a complex genetic trait that involves multiple genetic loci. Recently, 44 loci associated with height were identified in Caucasian individuals by large-scale genome-wide association (GWA) st Show more

Height is a complex genetic trait that involves multiple genetic loci. Recently, 44 loci associated with height were identified in Caucasian individuals by large-scale genome-wide association (GWA) studies. To identify genetic variants influencing height in the Korean population, we analyzed GWA data from 8842 Korean individuals and identified 15 genomic regions with one or more sequence variants associated with height (P<1 x 10(-5)). Of these, eight loci were newly identified in Koreans (SUPT3H, EXT1, FREM1, PALM2-AKAP2, NUP37-PMCH, IGF1, KRT20 and ANKRD60). The 15 significant loci account for approximately 1.0% of height variation, with a 3.7-cm difference between individuals with < or =8 height-increasing alleles (5.1%) and > or =19 height-increasing alleles (4.2%). We also examined the associations between height loci and idiopathic short stature (ISS). Five loci (SPAG17, KBTBD8, HHIP, HIST1H1D and ACAN) were significantly associated with ISS (uncorrected P<0.05), indicating that height-associated genes in the adult population are involved in extreme cases of short stature in children. This study validates previous reports of loci associated with human height and identified novel candidate regions involved in human growth and development. Show less

no PDF DOI: 10.1038/jhg.2009.116

EXT1

👤 Sung-Wan Kim