Infant methylenetetrahydrofolate reductase 677TT genotype is a risk factorfor congenital heart disease

Objective: Recently, an association between the homozygous C677T mutation i n the methylenetetrahydrofolate reductase (MTHFR) gene in infants with cong enital neural tube defects or congenital oral clefts has been shown. Howeve r, no data are available so far with respect to the MTHFR 677TT genotype in children with underlying structural congenital heart disease (CHID). Metho ds: We investigated the MTHFR genotype in 114 Caucasian CHD patients aged n ewborn to 16 years (median 0.6 years; 53% male) and in 228 age- and sex-mat ched healthy controls. Results: In childhood patients with CHD the homozygo us MTHFR 677TT genotype was found in 21 out of 114 subjects (18.4%) compare d with 21 out of 228 controls (9.2%; odds ratio (OR) 2.2, 95%-confidence in terval (CI) 1.2-4.3; P=0.027). In patients with pulmonary valve stenosis, h ypoplastic left heart syndrome, coarctation of the aorta, aortic valve sten osis or subaortic stenosis the frequency of the TT genotype varied between 38 and 67% with corresponding ORs from 6.1 (CI, 1.4-27.5; P=0.034) to 20.4 (Cl, 1.8-235.0; P=0.025), whereas in other structural CHD the frequency of this genotype was not significantly different from the controls. Conclusion s: With the present study we can show for the first time that the embryonal MTHFR 677TT genotype is significantly associated with the development of s tructural congenital heart malformations during early pregnancy. It remains to be clarified, whether this genotype is at least a risk marker or a risk factor for structural congenital heart malformations. (C) 2001 Elsevier Sc ience B.V. All rights reserved.