The genetic variants of solute carrier family 11 member 2 gene and risk of developing type-2 diabetes

Abstract

Type-2 diabetes (T2DM) is a metabolic disorder characterized by long-term insulin resistance, impaired insulin secretion from ${\upbeta }$-cells, and loss of beta cell mass and function. Inflammation and oxidative stress play a key role in the development of diabetes and are associated with insulin resistance. Notably, recent studies have demonstrated an association between body iron stores, insulin resistance and T2DM. Free iron, a powerful pro-oxidant molecule, is involved in oxidative stress, lipid peroxidation and endothelial dysfunction via its ability to generate free radicals. Specifically, the accumulation of iron in beta cells triggers oxidative stress and DNA damage, which have been reported to be associated with ${\upbeta }$-cell death and apoptosis. Solute carrier family-11 member-2 (SLC11A2) functions to transport ferrous iron and some divalent metal ions throughout the plasma membrane and across endosomal membranes. Functional polymorphisms in the SLC11A2 gene have been reported to cause excess storage of iron, resulting in iron overload. In this study, we evaluated the association between T2DM and SLC11A2 gene variants IVS4+44C/A, 1303C/A and 1254T/C by performing PCR-RFLP analysis on 100 T2DM patients and 100 healthy subjects. PCR products were digested with MnlI, MboI and SfanI restriction endonucleases and the products were then separated by 3% agarose gel electrophoresis. The genotype frequencies of the 1254T/C and 1303C/A SLC11A2 gene variants did not differ between healthy controls and T2DM patients ($P > 0.05$). But, in recessive model ($P = 0.037$) and homozygous CC genotype ($P = 0.030$) for IVS4+44C/A showed significant correlation with T2DM risk. It is thought that presence of C allele of IVS4+44C/A plays pathological roles.