Evaluation of C677T and A1298C polymorphisms of the MTHFR gene as maternal risk factors for Down syndrome and congenital heart defects

Abnormal folate/homocysteine metabolism due to polymorphisms in genes involved in this pathway has been implicated as an etiologic factor in Down syndrome (DS). This case–control study aimed to evaluate the effect of maternal C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) as risk factors for the development of DS and congenital heart defects (CHD). The distribution of these genotypic variants was similar between mothers of children with DS (n = 239) and control mothers of normal children (n = 197), but the combined genotypes 677CT or TT and 1298AA increased the risk of having offspring with DS (OR = 1.99; 95% CI 1.11–3.55). The presence of the 677T allele in case mothers resulted in a 2.07‐fold higher odds of CHD in the offspring (P