Association between 5,10-methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and conotruncal heart defects.

Reports related some polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) to folate-dependent neural tube defects. In view of the common origin of the cells involved both in neural tube closure and heart septation, we analyzed the MTHFR C677T and A1298C polymorphisms in mothers of children with conotruncal heart defect (CD) and in their offspring to evaluate the association between the MTHFR genotype and the risk of CD. We genotyped 103 Italian mothers with CD offspring, 200 control mothers, 103 affected children and their fathers by restriction fragment length polymorphism analysis. No increased risk was observed for the prevalence of the 677TT genotype by itself in affected children and in their mothers. The combined maternal 677TT/1298AA and 677CC/1298CC genotypes have odds ratio of 1.73 and 1.85, respectively. The prevalence of 1298CC genotype in the affected children gives odds ratio of 1.90, that becomes 2.31 for the 677CC/1298CC genotype. However, none of the odds ratios was statistically significant. We observed a higher frequency of the 677T allele in Italy than in other European countries. No association has been demonstrated between the 677TT MTHFR genotype and CD.