© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Infant methylenetetrahydrofolate reductase 677TT genotype is a risk factor for congenital heart disease
aInstitute of Clinical Chemistry and Laboratory Medicine and Institute of Atherosclerosis Research, University Hospital Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany
bDepartment of Pediatric Cardiology, University Hospital Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany
cChildrens Hospital Lachnerstrasse, Munich, Germany
dDepartment of Pediatrics, University Hospital Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany
eDepartment of Pediatric Hematology/Oncology, University Hospital Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany
* Corresponding author. Tel./fax: +49-251-834-7227 junkerr{at}uni-muenster.de
Objective: Recently, an association between the homozygous C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in infants with congenital neural tube defects or congenital oral clefts has been shown. However, no data are available so far with respect to the MTHFR 677TT genotype in children with underlying structural congenital heart disease (CHD). Methods: We investigated the MTHFR genotype in 114 Caucasian CHD patients aged newborn to 16 years (median 0.6 years; 53% male) and in 228 age- and sex-matched healthy controls. Results: In childhood patients with CHD the homozygous MTHFR 677TT genotype was found in 21 out of 114 subjects (18.4%) compared with 21 out of 228 controls (9.2%; odds ratio (OR) 2.2, 95%-confidence interval (CI) 1.2–4.3; P=0.027). In patients with pulmonary valve stenosis, hypoplastic left heart syndrome, coarctation of the aorta, aortic valve stenosis 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 (CI, 1.8–235.0; P=0.025), whereas in other structural CHD the frequency of this genotype was not significantly different from the controls. Conclusions: With the present study we can show for the first time that the embryonal MTHFR 677TT genotype is significantly associated with the development of structural 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.
KEYWORDS Congenital defects; Developmental biology; Coronary disease; Gene expression
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