👤 Lanqiong Xue

The apolipoprotein (apo) AI/CIII/AIV/AV cluster genes are expressed at different levels in the liver and intestine. The apoCIII enhancer, a common regulatory element, regulates the tissue-specific expression of apoAI, apoCIII, and apoAIV but not apoAV. To study this regulation at the chromatin level, the histone modifications and intergenic transcription in the human apoAI/CIII/AIV/AV cluster were investigated in HepG2 and Caco-2 cells and in the livers of transgenic mice carrying the human gene cluster constructs with or without the apoCIII enhancer. We found that both the promoters and the intergenic regions of the apoAI/CIII/AIV genes were hyperacetylated and formed an open subdomain that did not include the apoAV gene. Hepatic and intestinal intergenic transcripts were identified to transcribe bidirectionally with strand preferences along the cluster. The deletion of the apoCIII enhancer influenced both histone modification and intergenic transcription in the apoAI/CIII/AIV gene region. These results demonstrate that the apoCIII enhancer contributes to the maintenance of an active chromatin subdomain of the apoAI/CIII/AIV genes, but not apoAV. Show less

To investigate the association between the apolipoprotein A5(APOA5) -1131T/C polymorphism and premature coronary heart disease in northern Chinese Han population. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis (PAGE), we analyzed the genotype and allele distribution in 140 patients with premature coronary heart disease diagnosed by coronary angiography and 156 healthy controls. The levels of serum lipid profiles were also studied by biochemical methods. The allele frequency of APOA5-1131T/C polymorphism in the premature coronary heart disease group was significantly higher (43.2% vs. 33.0%, P=0.011) than that in the control group. Compared with TT homozygotes, CC homozygotes exhibited a 2.809-fold (95% CI 1.331-5.927) increased risk of developing premature coronary heart disease. Logistic regression analysis found that this correlation was independent of sex, age, body mass index (BMI), smoking history as well as serum total cholesterol(TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels; In premature coronary heart disease group, the triglyceride(TG) level in CC homozygotes was significantly higher than those in TC heterozygotes or TT homozygotes. The APOA5-1131T/C polymorphism has influence on serum TG level, and the APOA5-1131C allele is associated with the development of premature coronary heart disease in northern Chinese Han population. Show less

ApoAV, a newly discovered apolipoprotein, plays a key role in human triglyceride homeostasis; however, the structure-function correlation of apoAV is not clearly understood. To explore the relationship, wild type and six deletion mutants, that is (AV (Delta(1-51)), AV (Delta(51-128)), AV (Delta(132-188)), AV (Delta(192-238)), AV (Delta(246-299)), AV (Delta(301-343))), of human apoAV expressed in Escherichia coli were studied. All the deleted regions together encompass almost the entire 343 amino acid sequence of wild type apoAV. Circular dichroism spectroscopy showed that the alpha helical content of lipid-free wild type apoAV was 46%. In comparison with wild type apoAV, AV (Delta(192-238)) and AV (Delta(301-343)) displayed significantly decreased lipid binding activities, confirming the importance of these two regions in lipid binding function of apoAV. While, the LPL activation function of apoAV remarkably impaired after deletion of residues 192-238. These findings suggested that the domain (192-238) is absolutely necessary for apoAV in lipid binding and lipoprotein lipase activation. Show less

To investigate the association between the -1131T/C and 56C/G polymorphism in the APOA5 gene as well as the -482C/T in the APOC3 gene and susceptibility to coronary artery disease (CAD) in a Chinese Han population. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis (PAGE) methods, we analyzed the genotypes in 312 CAD patients diagnosed by angiography and 317 healthy controls. The levels of serum lipid profiles were also studied by biochemical methods. The frequency of the APOA5 -1131 C allele in CAD patients was significantly higher than that of the control group (39.9% vs. 33.3%, P = 0.02). Compared with the wild type TT, CC homozygotes had a significantly increased CAD risk (OR = 1.93 and OR = 1.80 using unadjusted and adjusted logistic regression models, respectively). This association still existed after adjustment for the APOC3-482 variant. The APOA5-1131C allele also showed a correlation with increasing plasma TG levels (P < 0.01). The APOA5-1131T/C polymorphism but not APOC3-482C/T might contribute to an increased risk of CAD among Chinese accompanied by an elevation of serum TG levels; this effect was found to be independent of the APOC3-482C/T variant. Show less

Two polymorphisms, apolipoprotein A5 (APOA5) -1131T>C and apolipoprotein C3 (APOC3) -482C>T, were examined in a healthy Chinese group. Analysis of covariance (ancova) showed that both -1131T>C and -482C>T minor alleles were associated with triglyceride (TG)-raising effects (p < 0.001 and p = 0.012, respectively) after adjustment of sex, age, and body mass index (BMI). Moreover, -1131T>C minor alleles were also found to be associated with total cholesterol (TC)-raising effects (p = 0.045). However, the relationship between -482C>T minor alleles and TC-raising effects was not observed after adjustment of sex, age, and BMI. By contrast, significant inverse associations were noted between minor alleles (-1131T>C and -482C>T) and high-density lipoprotein cholesterol (HDL-C) concentrations (p = 0.021 and p = 0.021, respectively). Linear regression analysis showed that the effects of -1131T>C and -482C>T polymorphisms on TG and HDL-C (0.001 and 0.008; 0.041 and 0.005, respectively) are independent and additive and that -1131T>C can seriously affect the levels of TG (0.001 vs 0.008). The additive effect of the two polymorphisms was confirmed further by haplotype analysis. Our results strongly support that the two single nucleotide polymorphisms, -1131T>C in APOA5 and -482C>T in APOC3, are related to the levels of serum TG and HDL-C and those of other several lipids and lipoproteins in the Chinese population. Show less