RESUMO
The vitamin K epoxide reductase complex subunit 1 (VKORC1) gene is expressed in many tissue types, and encodes the VKORC1 protein, which is a key enzyme in the vitamin K cycle. Although researchers have focused on the effects of vitamin K on glucose metabolism, and on its role in the development of type 2 diabetes (T2DM), no consensus has yet been reached. Therefore, here we aimed to investigate the association between VKORC1 variants and the risk of T2DM. The 3673G / A (rs9923231) and 9041G / A (rs7294) VKORC1 variants were investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 100 control individuals and 100 patients with T2DM. The genomic regions were amplified by PCR; amplicons were digested using the AciI and NciI enzymes and visualized by agarose gel electrophoresis. The genotype frequencies of the 3673G / A variants were GG (22%), GA (56%), and AA (22%) in the control group and GG (19%), GA (52%), and AA (29%) in patients with T2DM (p > 0.05). The genotype frequencies of the 9041G / A variants were GG (37%), GA (53%), and AA (10%) in the control group and GG (46%), GA (45%), and AA (9%) in patients with T2DM (p > 0.05). In conclusion, we found no significant correlation between the control group and patients with T2DM, with regard to the different genetic models of the 3673G / A and 9041G / A variants. These data suggest that these VKORC1 gene variants may not be linked to T2DM.
RESUMO
Type-2 diabetes (T2DM) is a metabolic disorder characterized by long-terminsulin resistance, impaired insulin secretion from ß-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 ß-cell death and apoptosis. Solute carrier family-11 member-2 (SLC11A2) functions to transport ferrous iron and some divalent metal ions throughout the plasmamembrane and across endosomalmembranes. 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, inrecessive 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.