The effect of NR4A3-rs12686676 and XBP1-rs2269577 polymorphisms on type 2 diabetes mellitus susceptibility in an Iranian population: Case-control study

Abstract

Many genes with different impacts on β-cell function, have been known as Type 2 diabetes mellitus (T2DM) risk genes. The purpose of this investigation was the evaluation of the potential correlation between rs12686676 and rs2269577 common polymorphisms of NR4A3 and XBP1 genes which are linked to β-cell function, and risk of T2DM in an Iranian population. In the present case-control investigation, 350 people affected by T2DM and 350 subjects in control group genotyped for NR4A3-rs12686676 by Tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method and XBP1-rs2269577 polymorphisms by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. According to results, no correlation between T2DM risk and NR4A3-rs12686676 polymorphism was found. However, we observed that CG genotype of XBP1-rs2269577 polymorphism could significantly decrease T2DM risk (OR = 0.6, 95%CI: 0.40–0.89, P = 0.01). Moreover, we detected that XBP1-rs2269577 SNP was related to the decreased risk of T2DM in dominant genetic model (OR = 0.5, 95%CI: 0.40–0.88, P = 0.01). In conclusion, there was no connection among pathogenesis of T2DM risk and NR4A3-rs12686676 polymorphism, however we found that heterozygote genotype (CG) of XBP1-rs2269577 SNP could decrease risk of T2DM in an Iranian population. Our result is the first report to show the protective role of rs2269577 SNP on diabetes risk.