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Original Article

JCDR. 2011; 2(3): 156-163

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

V. V. Ravi Kanth, Jaya Prakash Golla, B. K. S. Sastry, Sudhir Naik, Nitin Kabra,Madireddi Sujatha.


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.

Key words: Hyperhomocysteinemia, methionine synthase, methylenetetrahydrofolate reductase, polymorphisms, premature coronary artery disease

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