Genetic interactions between MTHFR (C677T), methionine synthase (A2756G, C2758G) variants with vitamin B12 and folic acid determine susceptibility to premature coronary artery disease in Indian population

Abstract

Background:Researchers have determined that Indians face a higher risk of heart disease, despite the fact that nearly half of them are vegetarians and lack many of the other traditional risk factors. In the below-30 age group, coronary artery disease mortality among Indians is three-fold higher than in the whites in United Kingdom and ten-fold higher than the Chinese in Singapore. High levels of homocysteine have been widely linked to the early onset of heart diseases in other populations, although a definite proof among Indians is lacking, which needs to be investigated by way of screening for factors responsible for high homocysteine levels.Objective:To screen for genetic factors responsible for hyperhomocysteinemia and the risk for premature coronary artery disease.Materials and Methods:A total of 100 individuals with proven premature coronary artery disease and 200 age-and-sex matched controls were screened for polymorphisms in Methylenetetrahydrofolate reductase (MTHFR) (C677T) Methionine synthase (MS) genes (A2756G, C2758G), and the B12 and Folate levels were estimated.Results:Results from the mutational analysis revealed that in the study group, seven individuals had a polymorphism for the C677T allele in the MTHFR gene (one homozygous and six heterozygous) (Fischer's Exact test P > 0.046) (OR: 0.2711 95% CI 0.0774 to 0.9491). Six were heterozygous for the A2756G polymorphism in the MS gene (Fischer's Exact test P > 0.0012). None showed a polymorphism at the C2758G allele in the MS gene. Four controls showed heterozygosity for the C677T polymorphism and none for the MS gene. The B12 and Folate levels were significantly lower in the study group as compared to the controls.Conclusions:It is important to know which factors determine the total homocysteine concentrations. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the total homocysteine concentrations, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors.

Epigenetic regulation of inflammation in stroke

“… 79 MHTFR is an enzyme responsible for the catalytic regeneration of methionine, which eventually is required as a methyl donor for DNA methylation. 80 For many years, it has been widely investigated that individuals exhibiting polymorphism of C677 > T demonstrate hyperhomocysteinemia, a condition characterized by accumulation of homocysteine, a product formed following DNA methylation. 80 MHTFR is responsible for the reconversion of homocysteine to methionine.…”

“… 80 For many years, it has been widely investigated that individuals exhibiting polymorphism of C677 > T demonstrate hyperhomocysteinemia, a condition characterized by accumulation of homocysteine, a product formed following DNA methylation. 80 MHTFR is responsible for the reconversion of homocysteine to methionine. 81 However, individuals possessing this genetic variant lack the ability to regenerate the methyl reservoir, leading to the build-up of homocysteine.…”

Newer perspectives of coronary artery disease in young

“…Some of the newer risk factors are discussed in the review. Polymorphisms in cholesterol ester transfer protein ( CETP ) gene, hepatic lipase gene, lipoprotein lipase gene, C-reactive protein gene, apo A1 gene, apo E gene, apo B , hypoxia inducible factor 1 alpha gene, factor 5 leiden, Methylene tetrahydrofolate reductase ( MTHFR ) gene and methionine synthase gene have been associated with premature CAD[34-38]. …”

Impact of Genetic Polymorphism of methylenetetrahydrofolate reductase C677T on Development of Hyperhomocysteinemia and Related Oxidative Changes in Egyptian β-Thalassemia Major Patients

“…This can lead to elevated hcy which acts as prooxidant, generates free radicals by auto-oxidation, induces lipid peroxidation [ 8 ], decreases endothelial NO and causes endothelial cell damage [ 9 ]. Hhcy has been claimed to have a part in the aetiopathogensis of several disorders including most importantly cardiovascular and peripheral vascular diseases [ 10 ].…”