Infant methylenetetrahydrofolate reductase 677TT genotype is a risk factor for congenital heart disease.
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.
Junker
R
R
Institute of Clinical Chemistry and Laboratory Medicine and Institute of Atherosclerosis Research, University Hospital Münster, Albert-Schweitzer-Strasse 33, 48149, Münster, Germany. junkerr@uni-muenster.de
Kotthoff
S
S
Vielhaber
H
H
Halimeh
S
S
Kosch
A
A
Koch
H G
HG
Kassenböhmer
R
R
Heineking
B
B
Nowak-Göttl
U
U
D000293:Adolescent; D001017:Aortic Coarctation / Q000235:genetics; D001024:Aortic Valve Stenosis / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D021922:Discrete Subaortic Stenosis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011666:Pulmonary Valve Stenosis / Q000235:genetics
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)