Background: Congenital heart defects (CHD) are present in most, but not all, cases of Down syndrome (DS). The presence of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms has been reported as a risk factor for CHD in DS. The aims of the present study were to assess (i) the frequency of MTHFR C677T and A1298C polymorphisms in DS individuals in the Croatian population; (ii) the relationship between the two maternal MTHFR polymorphisms and CHD-affected DS children; and (iii) the transmission frequencies of the variant alleles of the two MTHFR polymorphisms in CHD-affected DS.
Methods: The study population included 112 DS subjects and 221 controls. CHD were present in 48% of the DS subjects (54/112). The mothers of 107 DS individuals were available for the study; none was a periconceptional folic acid user. Allele transmission was analyzed in 34 complete parent-offspring triads.
Results: The frequencies of the allele, individual, and combined genotypes of MTHFR C677T and A1298C in DS subjects were not statistically different compared to the normal healthy Croatian controls. The maternal MTHFR polymorphisms were not found to be a risk factor for DS-related CHD. The allele transmission of the two MTHFR polymorphisms showed no deviations from random segregation.
Conclusions: Because the fetus is lost in a great proportion of trisomy 21 pregnancies, both maternal and fetal, not only live-born MTHFR C677T and A1298C, as well as maternal nutrition and lifestyle during pregnancy, should be analyzed to asses the impact on CHD in DS.
© 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.