Polymorphisms in folate-metabolizing genes as risk factors for congenital heart defects in Down syndrome in Egypt

Objectives: Down syndrome (DS) may be associated with congenital heart defects (CHD). Folate-metabolizing genes have been suspected as risk factors in DS and in CHD. We investigated the role of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and methionine synthase (MTR) A2756G polymorphism as risk factors for CHD in DS offspring. Material and Methods: This study included 116 DS children and their Egyptian mothers. Atrial septal defects, ventricular septal defects and patent ductus arteriosus were the defects considered. Mothers were divided into CHD-DS mothers and normal hearts-DS mothers. The analysis of MTHFR C677T and A1298C polymorphisms and MTR A2756G polymorphism was performed by PCR-RFLP. Allele/genotype frequencies were determined. Odd ratios and 95% confidence intervals were measured. Results: The distribution of different genotypes and allele frequencies of the three polymorphisms showed no significant differences between both groups of DS mothers, however, the genotypes of both MTHFR 677T and MTR 2756A together showed a significant p-value (0.035), but with an odd ratio of 0.39 (95% CI: 0.09-1.4). Conclusion: According to the results, MTR A2756G polymorphism and MTHFR C677T and A1298C polymorphisms could not be considered as maternal risk factors in Egyptian mothers for CHD in DS offspring. Further studies in different populations are needed.