ASSOCIATION OF ANTIOXIDANT GENE VARIANTS WITH TYPE 2 DIABETES MELLITUS IN DIFFERENT ETHNIC GROUPS
Pushpank Vats, Atar Singh Kushwah and Monisha Banerjee*
ABSTRACT
Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder resulting from oxidative stress due to impairment in antioxidant enzymes and their activities against reactive metabolites (RMs). The glutathione-S-transferases (GSTs) are dimeric cytosolic xenobiotic-metabolizing enzymes that catalyze the conjugation of active xenobiotics to glutathione (GSH). GST M1, T1 and P1 have been reported to be involved in T2DM development and related complications. Once formed, O2•-is dismutated enzymatically to H2O2 and oxygen by superoxide dismutase (SOD) antioxidants which include intracellular (CuZn-SOD), mitochondrial (Mn-SOD), and extracellular (EC-SOD) enzymes. Glutathione peroxidases (GPx) are selenocysteine-containing enzymes that catalyze the reduction of H2O2 and lipid hydroperoxides to H2O and lipid alcohols respectively in a reaction that utilizes glutathione (GSH) as a reducing co-substrate. GPx-1 is a ubiquitous antioxidant enzyme whose deficiency has been shown to promote endothelial dysfunction, heart failure and abnormal structural changes in vasculature and myocardium. Antioxidant gene polymorphism studies are a comprehensive way of understanding the stress sensitive pathways. Several groups all over the world are working to understand the association of T2DM with genetic variants in antioxidant genes. The present review has been undertaken to explore the association of antioxidant gene polymorphisms in various populations of different ethnicities. This will provide an understanding of the role of antioxidant genes in T2DM risk. Association of single nucleotide polymorphisms (SNPs) in antioxidant genes will help to identify risk genotypes/haplotypes for disease susceptibility and enable the development of prognostic markers for T2DM, a step towards personalized medicine.
Keywords: Type 2 Diabetes Mellitus, Oxidative Stress, Glutathione-S-Transferases, Polymorphisms, Superoxide Dismutase, Glutathione peroxidases.
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