Investigation of anti-glycation role of Glyoxalase 1 (GLO1) gene with increase susceptibility to Type II Diabetes Mellitus

Abstract

Type II Diabetes Mellitus (T2DM) is a global cause of increase mortality and morbidity. It is characterized mainly by high glucose index (hyperglycaemia). Moreover, hyperglycaemia is involved in enhanced accumulation of advance glycation end products (AGEs) in body. Detoxification of advanced glycation end products is carried out by glyoxalase system. Glyoxalase system maintains homeostasis of advance glycation end products (AGEs) by recycling methylglyoxal (MGO; a precursor to AGEs formation). The conversion of MGO to D-lactate is carried out chiefly by two enzymes. Glyoxalase 1 (Glo1) is given more importance owing to its rate limiting ability. Genetic variations like single nucleotide polymorphisms (SNPs) in the enzyme coding or regulatory genes like in Glyocalase1 gene (GLO1) might disturb the functional aspect of enzyme Glo1. This research study aimed to use computational bioinformatic tools and High-Resolution Melting (HRM) analysis to predict and validate functionally significant SNPs in GLO1 gene associated with T2DM. For computational analysis of non-coding regulatory single nucleotide polymorphisms (SNPs), data was collected and analysed from online databases and web-based tools. In-silico screening gave seven SNPs expected to affect gene function and advance glycation end products accumulation (AGEs), increasing susceptibility to Type II Diabetes Mellitus. Genetic association studies for glyoxalase 1 gene SNPs were done by High-Resolution Melting analysis. High Resolution melt curve analysis of Glyoxalase 1 gene SNP rs1038747749 authenticate its significant association with disease pathogenesis, whereas SNP rs753587598 showed no significant association, further studies can be done to check their association with large sample size.