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

Abstract

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.