7th Indo Global Diabetes Summit and Medicare Expo
ACS Medical College and Hospital
Title: Association of genetic variants with markers of oxidative stress and intimal medial thickening in patients with type 2 diabetes mellitus and coronary artery disease
Biography: R Dhananjayan
Functional polymorphism in genes regulating one-carbon metabolism and deficiency of micronutrients such as folate, vit-B12, vit-B6 etc., perturbate one-carbon metabolism. Hence they are associated with elevated plasma homocysteine (HCY) and decreased functional folate, S-adenosyl methionine (SAM) and glutathione (GSH). Elevated HCY acts as pro-oxidant and found to generate free radicals by auto-oxidation, inducing lipid per-oxidation, causes endothelial cell damage and also perturbing hemostasis. Decreased levels of folate are associated with defective synthesis of purines and uracil mis-incorporation in DNA. Decreased SAM with increased S-adenosyl homocysteine (SAH) blocks methyl transferases, leading to decreased cellular methylation and is associated with altered gene expression. The above events are likely to lead atherosclerosis and arterial thrombosis. Several SNPs were reported in genes regulating the one-carbon metabolic pathway interfere with the uptake of folate, folate carrier, DNA synthesis, synthesis of methyl tetra-hydrofolate, remethylation of HCY and reductive methylation of cobalamin. Among different polymorphisms of one-carbon metabolism, i.e., glutamate carboxypeptidase II (GCPII C1561T), reduced folate carrier 1 (RFC G80A), serine hydroxyl methyl transferase 1 (cSHMT C1420T), thymidylate synthase (TYMS 5’UTR) 28bp tandem repeat, methylene tetrahydro-folate reductase (MTHFR C677T) and 5-methyltetrahydrofolate homocysteine S-methyl transferase (MTR A2756G), the extensively studied polymorphisms in CAD are GCPII C1561T, MTHFR C677T and MTR A2756G. MTHFR C677T has been observed to be associated with independent risk for CAD in the subjects with low folate status. The increased oxidative stress is one of the main factors in etiology and complications of diabetes mellitus (DM). GSH is the major cellular antioxidant, detoxifies ROS, reduces peroxides and detoxifies multiple compounds through glutathione-S-transferase (GST) conjunction. GSTs defend cells against a wide variety of toxic insults from chemicals, metabolites and oxidative stress. An important condition affecting GST expression is oxidative stress, usually observed in DM. Folate and its metabolites play an important role in the synthesis, repair and methylation of DNA and hence any aberration in this metabolic pathway may lead to hyper homocysteinemia which might contribute to etiology of CAD. Xenobiotic metabolism is the principle pathway that scavenges lipophilic xenobiotic agents and certain endogenous metabolites. Any alteration in this metabolic pathway prevents scavenging and increase reactive intermediates that have the potential of oxidative damage.