Association of Perilipin and Insulin Receptor Substrate-1 Genes Polymorphism with Lipid Profiles, Central Obesity, and Type 2 Diabetes in a Sample of an Iranian Population

Background Since insulin receptor substrate-1 (IRS-1) is the main substrate of the insulin receptor tyrosine kinase and has been detected to activate phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1 gene is a possible candidate for development of type2 diabetes, insulin resistance, and obesity. Preilipin (PLIN) coats intracellular lipid droplets and modulates adipocyte lipolysis. Objectives In this study, we investigated whether insulin receptor substrate-1 (IRS-1) and Perilipin (PLIN) genes polymorphism were associated with Type 2 diabetes (T2D), obesity, and lipid profiles in a sample of the Iranian population (Southeast of Iran). Methods In this randomized case-control study (Feb, 2016 to Sep, 2016), we genotyped 200 patients with T2D and the same number (200) of controls by using the combined nested-polymerase chain reaction (PCR) as well as the amplification refractory mutation system (ARMS)-PCR for IRS-1 variant and Tetra-ARMS-PCR for PLIN variant in southeast Iran (Zahedan). Results The polymorphism of 4578621 in the PLIN gene was associated with T2D. GG genotype and G allele at rs4578621of PLIN gene were significantly higher in patients than in controls (for the G allele: OR = 2.31, 95%CI = 1.55 - 3.46, P < 0.0001; for the GG genotype: OR = OR = 2.67, 95%CI = 1.71-4.19, P<0.0001). Furthermore, women with fast blood glucose (FBG) < 110 mg/dL are in protection of diabetes (P < 0.001, OR = 0.561 (0.430 - 0.733), for women, (P = 0.002, OR = 0.481 95%CI: 0.305 - 0.756), for FBG, (P = 0.002, OR = 0.591, 95%CI = 0.422 - 0.829), for triglyceride (TG) < 130 mg/dL, and (P = 0.001, OR. = 0.563, 95%CI = 0.407 - 0.780) for TG ≥ 130. On the other hand, the polymorphism of 2943641 in IRS-1 gene was not associated with T2D (P = 0.08). However, the frequencies of the risk A allele at rs29436411of IRS-1 was significantly higher in patients than in controls (G allele: OR = 0.55, 95% CI = 0.36 - 0.848, P = 0.0086). Also detected, BMI ≥ 25 is a risk factor for diabetes in rs29436411of IRS-1 gene (P = 0.024, OR = 1.604 95%CI = 1.063 - 2.420). Conclusions The rs2943641 polymorphism of the IRS-1 gene is a major genetic determinant of obesity but not Type 2 diabetes and lipid profiles. The rs4578621 polymorphism of the PLIN gene related with T2D and TG but not obesity.