The A1298C Methylenetetrahydrofolate Reductase Gene Variant as a Susceptibility Gene for Non-Syndromic Conotruncal Heart Defects in an Indian Population.

Conotruncal heart defects (CTHDS) are a subgroup of congenital heart malformations that are considered to be a folate-sensitive birth defect. It has been hypothesized that polymorphisms in genes that code for key enzymes in the folate pathway may alter enzyme activity, leading to disruptions in folate metabolism and thus may influence the risk of such heart defects. This study was designed to investigate the association of six selected folate-metabolizing gene polymorphisms with the risk of non-syndromic CTHDs in an Indian population. This was a case-control study involving 96 cases of CTHDs and 100 control samples, ranging in age from birth to 18 years. Genotyping using Sanger sequencing was performed for six single nucleotide polymorphisms of genes involved in folate metabolism. Logistic regression analyses revealed that for the 5,10-methylenetetrahydrofolate (MTHFR) A1298C polymorphism, the CC variant homozygote genotype was associated with a significantly increased risk of CTHDs. The results of this study support an association between the inherited MTHFR A1298C genotype and the risk of CTHDs in an Indian population.