Genetic polymorphism of glyoxalase I gene (A419C and C-7 T) and nephropathy risk in patients with type 2 diabetes mellitus among north Indian population: A case-control study

Abstract

BackgroundThe global burden of Diabetic nephropathy is rising and eventually leads to chronic kidney disease. Methylglyoxal (MGO) is an antecedent to advanced glycation end products (AGEs), implicated in diabetes mellitus microvascular complications. Glyoxalase I (GLO1), is the primary enzyme responsible for metabolizing methylglyoxal (MG). Any genetic variants of GLO1 may have a significant impact on the development of diabetic microvascular complications. ObjectivesTo determine the association of rs1049346 and rs4746 (rs2736654) of Glyoxalase I gene polymorphism in type 2 Diabetes patients (T2DM) with nephropathy risk. Materials and methodsThe case-control study included a hundred T2DM with nephropathy and a hundred healthy controls. The TaqMan single nucleotide polymorphism genotyping assays were performed using Real-Time PCR to assess the genotype frequencies. The circulating levels of GLO-1 activity, MGO, CML and CEL were estimated using Enzyme-linked immunosorbent assay (ELISA). Results and discussionWe observed increased serum levels of MGO, AGEs and decreased GLO-1 activity in diabetic nephropathy when compared to control. The patients carrying the CC genotypes (CC) and allele frequency of GLO-1 (rs1049346) were associated with nephropathy risk in T2DM patients (p < 0.024). We found no association of rs4746 with nephropathy risk in patients with T2DM. The patients with the CC + CT genotype showed lower GLO-1 activity and increased MGO levels when compared to homozygous wild-type. The CA haplotype significantly increased the risk of T2DM nephropathy. ConclusionPatients with T2DM who carry the variant CC genotype of rs1049346 (A > C) are at increased risk for developing nephropathy. The patients carrying the CC + CT genotype was associated with lower GLO-1 activity and increased MGO levels.