The Association Between genetic variations of KCNj11 gene and type 2 diabetes mellitus in a sample of Iraqi population.

Abstract

Background: Type 2 diabetes mellitus is a polygenic disorder that develops as a result of a complex interaction between multiple genes and environmental factors. KCNJ11 gene encodes a Kir6.2 protein which forms the inner section of the potassium channels in pancreatic beta cells. Methods: This case-control study involved 300 T2DM patients and 300 healthy controls. The KCNJ11 rs5215 and rs5210 polymorphism was genotyped by Restriction Fragment Length Polymorphism (RFLP).  Results  : Hardy Weinberg equation statistics of KCNJ11 rs5210 (A/G) SNP genotypes among patients, control subjects highly significant (p < 0.001). Comparison of KCNJ11 rs5210 (A/G) SNP genotypes the codominance model, the additive model The recessive model and has shown no significant variation between control and patient groups (p = 0.564), (p = 0.806)and (p = 0.284) respectively. confirmed the lack of significant association (p = 0.589). Analysis of alleles has shown no significant association (p = 0.432). Comparison of BMI and HDL is significant to KCNJ11 rs5210 (A/G) SNP genotypes based on codominance model and other biochemical is not . Hardy Weinberg equation statistics of KCNJ11 rs5215 (C:I /T:V) SNP genotypes among patients, control highly significant (p < 0.001). The codominance model has shown no significant difference (p =0.835). The dominant model, the recessive model and the additive model has shown no significant difference (p =0.581),(p =0.606) and (p =0.483). Allele analysis has shown no significant difference (p =0.463). Comparison of BMI and cholesterol is no significant to KCNJ11 rs5215 (C/T) SNP genotypes based on codominance model and other biochemical is significant. The association between risk of disease and haplotypes resulting from KCNJ11 rs5210 (A/G) versus rs5115 (C:I /T:V) interaction is H 1 , H2 haplotypes was associated with highly significant risk of disease (p = 0.004) OR of 1.64, (p < 0.001) with an OR of 0.35. H 3 haplotypes was associated with significant protection against the disease (p = 0.024) with an approximate OR of 0.69. The presence of H 4 haplotypes was associated with highly significant risk of the disease (p < 0.001) with an OR of 2.52. Conclusions: This study showed that rs5215and rs5210 polymorphism of the KCNJ11 gene is an important risk factor for type 2 diabetes mellitus in a sample of the Iraqi  population.  Aimed of study :This study was aimed to detect the relationship between  the rs5215and rs5210 polymorphism of the KCNJ11 associated with T2DM in Iraqi population ,what is the impact of haplotype analysis on the risk of T2DM  as well as the glycemic indices.