Association of a genetic variant in angiopoietin-like 3 with serum HDL-C and risk of cardiovascular disease: A study of the MASHAD cohort over 6 years.

BACKGROUND: Loss-of-function (LOF) variants of the angiopoietin-like 3 (ANGPTL3) gene are reported to be associated with serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations and thereby affect the risk of cardiovascular disease (CVD). OBJECTIVE: In the present study, we examined the association of rs10789117 in the ANGPTL 3 gene locus and the risk of CVD in the group of people who were part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. METHODS: One thousand and two healthy individuals enrolled in this study of whom 849 subjects were healthy and 153 subjects developed CVD outcomes after 6 years of follow-up. After a 12-h overnight fasting, 20 mL of blood samples were collected for the measurement of fasting blood glucose and lipid profile. DNA was extracted, and the Tetra-ARMS PCR (amplification refractory mutation system) was used for genotyping of rs10789117 in the ANGPTL3 gene. The genotype frequencies of the variant of rs10789117 in the ANGPTL3 gene were estimated using χ2 tests. Eventually, the statistical analysis was done by SPSS version 20. RESULTS: Individuals with AC/CC genotypes (rs10789117) were found to have to greater risk of CVD events compared to AA genotype (OR = 1.43, 95%CI = 1.01-2.02, p = 0.041). There was a 1.3-fold increase in cardiovascular events in individuals carrying the C allele of rs10789117 variant compared to non-carriers (OR = 1.32, 95%CI = 1.06-1.72, p value = 0.038). There were significant differences between different genotypes for serum triglyceride levels within the control group, but this difference was not significant in the group with CVD. Moreover, there was a significant association between CC genotype and CVD risk in the individuals with a normal serum HDL-C. CONCLUSION: We have found that a rs10789117 C>A in ANGPTL3 gene polymorphism was associated with incident CVD events, and this may be of value as a risk stratification biomarker in CVD in the Iranian population.

Association Between Retinoid X Receptor Gene Variants and Dyslipidemia Risk in an Iranian Population.

Background Dyslipidemia is a complex trait that is influenced by various genetic and environmental factors. While the exact cause of dyslipidemia is still unknown, some studies have shown that genetic factors such as single nucleotide polymorphisms (SNPs) have been primarily associated with dyslipidemia. Based on the available data, it appears that retinoid X receptor (RXR) genes are jointly or separately associated with lipid homeostasis and that SNPs may affect RXR gene functions in lipid metabolism. Methods To study the possible role of the RXR genes in genetic susceptibility of dyslipidemia, three selected polymorphisms, rs3132294 located in RXRA (RXR-alpha) gene and rs2651860 and rs1128977 located in RXRG (RXR-gamma) gene, were investigated in 391 individuals with the use of tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS PCR) method. Results For the rs3132294 SNP, the genotype frequencies in the case group were GG 58.5%, GA 33.2%, and AA 8.3%, and in the control group, they were GG 51.8%, GA 36.3%, and AA 11.9%. The genotype distribution of rs2651860 SNP in the case group were TT 43.2%, TG 52.1%, and GG 4.7%, and in the control group, they were TT 50.8%, TG 46.2%, and GG 3%. Genotype frequencies for the rs1128977 SNP in the case group were CC 34.7%, CT 47.6% and TT 17.7%, compared with CC 37.8%, CT 44.3%, and TT 17.9% in the control group. When the clinical characteristics of the case and control groups were stratified by allele carrier status for each SNP, the rs1128977 SNP was associated with increased levels of HDL-cholesterol, body mass index, waist circumference, and diastolic blood pressure (P< 0.05). In contrast, the alleles of the rs2651860 and rs3132294 SNP were not associated with an increased prevalence of dyslipidemia or clinical characteristics in the case group compared to the control group. Conclusion The present study suggests that rs1128977 SNP in the RXRG gene may affect the clinical characteristics in cases. However, further genetics association studies on large samples are required to validate our findings.