Polymorphism of Human Insulin Receptor INSR Gene Rs1366600 in Iraqi Patients with Type2 Diabetes Mellitus

Abstract

The aim of this study was to investigate the association of polymorphisms of human insulin receptor gene INSR rs1366600 to the susceptibility of type2 diabetes mellitus in diabetic patients from Wasit province using TaqMan SNP genotyping assay. A total of 80 participants (45 confirmed patients with type2DM and 35 healthy individuals as controls) were selected by using a convenient sampling method. The results of the current study displayed that in both in patients and control groups, the distribution frequencies of the genotypes and alleles of human insulin receptor gene rs1366600 A/G were not consistent with Hardy Weinberg equilibrium P<0.05. G allele is a major one in the studied groups. This allele is common in T2DM patients (65.56%) and controls (91.43%) with a highly significant difference, p-value =0.00012. The main genotype is GG in the patients and controls Groups. Notably, a significantly higher frequency of the homozygous AA genotype and heterozygous AG genotype was observed when T2DM patients were compared with controls 26.60% and15.62% respectively in patients vs. (2.85%) and(11.43%) in controls 3for each genotype respectively, p=0.0095. Moreover, frequency of homozygous GG genotype was lower when compared T2DM patients (57.78%) and healthy controls (85.72%) at tested position. These results suggest that the G allele might be a protective against the disease whereas the A allele may be considered as a risk factor in the disease. The association analysis revealed that the homozygous GG genotype reduces significantly the likelihood of contracting T2DM with OR= 0.2281 (CI95% [0.0747 to 0.6965]) p = 0.0095. The AA genotype increases the association significantly with T2DM with OR=12.3636 (CI95% [1.5208 to 100.5106]) ,p = 0.0187. The heterozygous genotype AG increases also the association with T2DM with OR=1.4276(CI95% [0.3826 to 5.3277]),p = 0.5962. The subgroup analysis displayed that the T2DM risk of females with 1366600A/G AA genotype was 2.6471 times higher than that in controls OR= 2.6471 (CI 95% [0.2481 to 28.2409]),p= 0.4203,. GG genotype decreases the probability of contracting the disease with OR = 0.6190 (CI 95% [0.1441 to 2.6594]) p = 0.5190. AG genotype increases slightly the association with T2DM with OR= 1.11 (CI95% [0.2047 to 5.7336], P = 0.9250. The polymorphism of INSR rs1366600 of the AA genotype increases significantly T2DM risk among the male patients OR= 22.4545 (CI95% [1.2129 to 415.6955]), p = 0.0367. The heterozygous AG genotype also increases the association with the disease OR= 2.4545 (CI95% [0.2347 to 25.6699]) ,p = 0.4534. While, the homozygous GG genotype decreases significantly the association with the disease OR= 0.0602 (CI95% [0.0069 to 0.5225]), p= 0.0108. In conclusion, human insulin receptor gene rs1366600 has possible roles in type2 diabetes mellitus susceptibility.