👤 Melika Fallah

FADS1 rs174556 polymorphism influences on dietary fats metabolism and type 2 diabetes (T2DM). This study aimed to compare the effect of three oils of sesame, canola and sesame-canola on cardio metabolic factors across genotypes of rs174556 variant in patients with type 2 of diabetes. This study was a randomized triple-blind three-way cross-over clinical trial. 95 Subjects with T2DM replaced their regular dietary oil with sesame oil, canola oil, or sesame-canola oil for three 9-week phases and completed the study. There were three anthropometric measurements, blood sampling and biochemical assessments at the beginning, middle, and at the end of each phase for assessments. Genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In the crude model, there was an interaction between consumed oils and rs174556 variant on serum concentration of Apolipoprotein A-I (ApoA-1). During intake of sesame oil, lower levels of triglycerides (TG) were observed in individuals with TT genotype compared to C allele carriers' allele, which remained significant in adjusted models. Compared to C allele carrier's, the people with TT genotype experienced significant increase and decrease in serum levels of HDL and TG, respectively in adjusted models. Also, the subjects who consumed sesame-canola oil had lower serum concentrations of fasting blood glucose than those who received sesame and canola oils, regardless of used oils and genotypes. FADS1 Gene variant (rs174556) might modify cardiometabolic changes following dietary vegetable oils. Larger longitudinal studies especially randomized clinical trials are needed to clarify these associations. Show less

Obesity has become a common global problem. Some obese people can be metabolically healthy. Gene-environment interaction can be important in this context. This study aimed to assess the interaction between dietary fat quality indices and the Melanocortin 4 receptor (MC4R) gene in metabolically healthy and unhealthy overweight and obese women. This cross-sectional study was conducted on 279 women with overweight and obesity. The definition of metabolically healthy and unhealthy phenotypes was done according to Karelis criteria. Dietary assessment was done using a 147-item validated semi-quantitative food frequency questionnaire and dietary fat quality was assessed by cholesterol-saturated fat index (CSI) and the ratio of omega-6/omega-3 (N6/N3) essential fatty acids. MC4R was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. A generalized linear model was used to evaluate the interaction between dietary fat quality indices and the MC4R gene in both crude and adjusted models. Study subjects with higher ratio of N6/N3 had higher homeostatic model assessment for insulin resistance (HOMA IR) index (P = 0.03) and other variables showed no difference according to the tertile of CSI and N6/N3. Participants with the C allele of MC4R rs17782313 had lower height (P < 0.001) and higher HOMA index (P = 0.01). We found that the CC genotype of MC4R interacts with the N6/N3 ratio on the metabolically unhealthy phenotype in the crude model (β = 9.94, CI 2.49-17.39, P = 0.009) and even after adjustment for all confounders (β = 9.002, CI 1.15-16.85, P = 0.02, β =  - 12.12, CI 2.79-21.46, P = 0.01). The data of this study can justify one inconsistency observed in society, regarding dietary recommendations about metabolic health status. Those with CC genotype, are more likely to have an unhealthy phenotype with an increase in N6/N3 as one fat quality indices than those who do not have CC genotype. We found the interaction of dietary fat quality indices such as N6/N3 and the MC4R gene in metabolically unhealthy overweight and obese women. Show less

Obesity is currently an international epidemic and metabolic derangements pose these individuals at greater risk for future morbidity and mortality. Genetics and environmental factors have undeniable effects and among genetic risk factors, FTO/CETP genes are important. The current study examines the interaction between obesity phenotypes and FTO/CETP SNPs and their effects on lipid profile changes. We selected 954 adult subjects from TCGS (47.9% male). Participants were stratified according to their BMI and presence of metabolic syndrome according to the Joint Interim Statement (JIS) definition. Nine selected polymorphisms from FTO/CETP genes were genotyped using Tetra ARMS-PCR method. After age and sex adjustment the interaction of 9 markers with lipid profiles among phenotypes were tested by PASW. In three main groups, HDL_C level had a strong significant association with CETP markers: (rs3764261, β(95% CI) - 0.48(- 0.61 to - 0.35), P = 1.0 × 10 In the present study, we investigated the association between obesity phenotypes and some variations in FTO/CETP genes for the first time. Our study showed that four markers in the first intron of the FTO gene should be the risk marker in MUHO participants. Level III, case-control study. Show less

Anaplastic thyroid carcinoma (ATC) is the most lethal malignancy in thyroid carcinomas. Long non-coding RNAs (lncRNAs) are a member of non-coding RNAs, regulating the expression of gene. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an onco-lncRNA that is overexpressed in several carcinomas including ATC. Evidence showed that MALAT1 has a crucial function in apoptosis, and cell cycle progression. In order to take advantage of 3D cell culture system in cancer investigation, we have used a 3D in vitro ATC model to determine the effect of dual MEK/Aurora kinase inhibitor BI-847325 anticancer drug on the fundamental molecular mechanisms of MALAT1-mediated gene regulation in ATC. In this study, ATC cell lines (C643 and SW1736) were grown in alginate scaffold. Encapsulated cells were treated by BI-847325. Changes in expression of MALAT1, Mcl1, miR-363-3p, and cyclinD1 were measured by qRT-PCR. MALAT1 gene expression following BI-847325 treatment was significantly downregulated in C643 and SW1736 cell lines. Reversely, miR-363-3p expression was significantly upregulated by BI-847325 in both ATC cell lines. Mcl1 expression was significantly downregulated after treatment in C643 cell lines. Moreover, the expression of this gene was not significantly reduced following BI-847325 treatment in SW1736 cell line. Additionally, cyclin D1 expression was significantly downregulated after treatment in both ATC cell lines. Altogether, the result of this study was the first report of MALAT1's molecular function in ATC and suggested that BI-847325 which inhibits both MEK and Aurora kinase family could be effective against ATC by regulating the genes involved in cell cycle and apoptosis including MALAT1and its downstream genes. Graphical abstract Schematic representation of the biological role of MALAT1 in cyclin D1, miR-363-3p and Mcl1 gene regulations. Stimulation of receptor tyrosine kinase (RTK) by growth factors (GFs) phosphorylates RAS that subsequently activates RAF. Then, RAF phosphorylates MEK. Consequently, activated MEK phosphorylates ERK downstream effector, leading to the MALAT1 gene expression. MALAT1 is a negative regulator of Mcl1 mRNA by sponging of miR-363-3p. In addition, MALAT1 leads to Axin1 and APC downregulation and Wnt/β-catenin signaling pathway activation. Stable β-catenin translocates from the cytoplasm to the nucleus and promotes cyclin D1 gene expression. Show less

Metabolic syndrome (MetS) is a multi-factorial disorder with five important components. A high triglyceride level combined with low HDL cholesterol has been reported to be associated with Apolipoprotein A5 (APOA5) gene variations. In this study, we aimed to determine the association of single nucleotide polymorphisms including: rs662799, rs3135506 and rs2075291 in the apolipoprotein A-V (APOA5) gene in relation to MetS component like triglyceride and HDL-C level in Tehran Lipid and Glucose Study (TLGS). Metabolic syndrome was defined according to ATPIII and phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS. Demographic, biochemical parameters and anthropometric variables were measured. Selected APOA5 gene polymorphisms were genotyped using PCR-RFLP method. From TLGS population, 947 adults, aged 19 - 70 years, were randomly selected and recruited into the study. Mean age, triglyceride and WC were higher and mean HDL was lower in MetS vs. non-MetS group. C allele in rs2075291 showed a significant association with MetS (OR: 2.38, 95% CI; 1.11 - 5.08, P = 1.5 ×10(-2)). The association was shown between higher serum triglyceride and the presence of T allele (P = 4.5 × 10(-4)) and also lower serum HDL-C and the presence of T allele (P = 1.6 × 10(-3)) in rs2075291. Also this association showed between raised waist circumference and C allele in rs3135506 (P = 3.5 × 10(-2) ) and raised systolic and diastolic blood pressure level and C allele of rs662799 (P = 4.5 × 10(-2)). According to the results, there is a relationship between lipid profile and studied polymorphism in the presence of metabolic syndrome. It seems that APOA5 rs2075291 could play an important role in triglyceride and HDL-C level in metabolic syndrome affected, while the association of APOA5 rs662799 polymorphism is still under debate. Show less

It is suggested that C771G (His241Gln) polymorphism of MLXIPL gene might be a genetic risk factor for coronary artery disease (CAD); therefore, the aim of the present study was to investigate the association between C771G polymorphism of MLXIPL gene and the pathogenesis of CAD in Iranian patients with coronary artery stenosis and control subjects. Two hundred and five patients with coronary artery stenosis and 195 healthy control subjects were included in this study. MLXIPL genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (RFLP). There was an association between the MLXIPL polymorphism and quantitative lipid traits in patient group. Distribution of the CC genotype of MLXIPL was more frequent in patients, (χ2=5.13; p<0.005) and after adjustment for classical CAD risk factors, the MLXIPL CC genotype was independently associated with CAD (OR=1.98, 95% CI, 1.12-4.11; p=0.02). Distribution of MLXIPL genotypes were significantly different as compared with the severity of stenosis (χ2=6.34; p<0.05). These results suggest that C771G polymorphism of MLXIPL gene is associated with stenosis and its severity. Show less