Common Variant (rs1111875) of HHEX Gene and Risk of Type 2 Diabetes Mellitus

Introduction: Type 2 diabetes (T2D) is a common, chronic, complex disorder. The risk of developing T2D is influenced by both genetic and environmental factors that interact in determining impaired β-cell insulin secretion and peripheral insulin resistance. HHEX gene is an excellent candidate susceptibility gene for T2D. The purpose of this study was to investigate the effect of rs1111875 of HHEX gene with the risk of T2D in a group of Iranian patients.Materials & Methods: 108 type 2 diabetes patients and 100 normal subjects were included. The rs1111875 polymorphism of the HHEX gene was determined by polymerase chain reaction and restriction fragment length polymorphism.Results: Frequencies of AA, GG and AG genotypes among the cases were 7.41%, 82.41% and 10.19% and in controls were 73% , 27% and 0% respectively. Frequency of G allele among cases was significantly higher than controls (87.5% vs 27% respectively, p<0.001). The odds ratio for G allele was 18.92 (p<0.001).Conclusion: Our study showed that rs1111875 polymorphism of HHEX gene can be associated with diabetes mellitus. The GG homozygote genotype of this polymorphism significantly increased the odds of diabetes mellitus. In addition, the allelic investigation showed that carriers of G allele had approximately 19 folds higher risk of developing diabetes mellitus compared to A allele carriers. Therefore, this allele can be a strong risk factor for diabetes mellitus.