The Relationship Between genetic variations of KCNQ1 with insulin resistance and type 2 diabetes in a sample of Iraqi population

Abstract

Background and objectives: Type 2 diabetes is a common complex disorder, characterized by chronic hyperglycemia as the result of an incapacity of the pancreatic beta cells to compensate for the degree of insulin resistance .Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1) have recently been reported to associate with type 2 diabetes. The present study was to investigate the impact of these KCNQ1 polymorphisms (rs2237892, and rsl51290) in Iraqi population. Methods: The study was conducted in 600 Iraqi population., This case-control study involved 300 T2DM patients and 300 healthy controls. The KCNQ1 (rs2237892, and rsl51290) polymorphism was genotyped by Restriction Fragment Length Polymorphism (RFLP).
Results: Hardy Weinberg equilibrium for KCNQ1 (rs2237892) control group, patients’ group and all subjects as a group possess highly significant deviation (p < 0.001), when the dominant, codominant, recessive and additive models were taken into account.. There was highly significant difference in mean BMI, cholesterol, triglyceride, LDL ,insulin and IR among CC, CT and TT genotypes groups (p <0.001), while There was significant difference in mean FBS,VLDL among CC, CT and TT genotypes groups (p = 0.020)and (p = 0.041) respectively also there was no significant difference in mean HDL among patients with CC, C/T and TT genotypes (p = 0.475). Hardy Weinberg equilibrium for KCNQ1( rsl51290) control group, patients’ group and all subjects as a group possess highly significant deviation (p < 0.001) ,when the dominant, codominant, recessive and additive models were taken into account. There was no significant difference in mean of BMI, FBS, cholesterol, HDL, LDL and VLDL among AA, AC and CC genotypes (p= 0.036, p= 0.186, p= 0.731, p= 0.054, p= 0.317, p= 0.521 respectively), while there was a highly significant difference in mean of triglyceride , IR and insulin among AA, AC and CC genotypes groups (p = 0.007), (p = 0.004 and p = 0.003). Haplotype analysis of the KCNQ1 SNPs showed a significant association with T2DM increase to develop the disease under H 4, while there was no association with the H 2. Haplotyping of KCNQ1 gene SNPs (rs2237892, and rsl51290). However, other models H1 and H3to explore highly significant association. Conclusion: This study showed that (rs2237892, and rsl51290) polymorphism of the KCNQ1 gene is an important risk factor for type 2 diabetes mellitus in a sample of the Iraqi population.