Association of the C677T methylenetetrahydrofolate reductase mutation with congenital heart diseases.
BACKGROUND
To investigate whether the cytosine-to-thymine mutation at base 677 of the gene for methylenetetrahydrofolate reductase (MTHFR) is associated with congenital heart diseases (CHD), using high throughput heteroduplex analysis based upon the powerful technique of denaturing high-performance liquid chromatography.


METHODS
We investigated the MTHFR genotype of a cytosine-to-thymine mutation at base 677 for 213 patients of CHDs as confirmed by cardiac catheterization and also for 195 healthy controls.


RESULTS
The overall genotype frequencies of the MTHFR C677T polymorphism were not significantly different between the CHD patients and the healthy control (P = 0.345). Furthermore, taking various subgroups of CHD patients into consideration, we noted a significantly increased proportion of homozygous TT genotypes for patients suffering from valvular pulmonary stenosis (PS) or pulmonary atresia with an intact ventricular septum (PA + IVS) (p = 0.0005). For patients revealing heterotaxy syndrome, a conotruncal anomaly including tetralogy of Fallot, an interruption of the aortic arch, persistent truncus arteriosus, and aortopulmonary window, no statistically significant difference existed.


CONCLUSIONS
The discrepancy in the distribution of MTHFR genotypes amongst various subtypes of CHD reflects some heterogeneity in the developmental mechanism of CHD. The increased percentage of homozygous TT genotypes might contribute to the pathogenesis of valvular PS and PA + IVS.
Lee
Chien-Nan
CN
Department of Obstetrics and Gynecology, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan.
Su
Yi-Ning
YN
Cheng
Wen-Fang
WF
Lin
Ming-Tai
MT
Wang
Jou-Kou
JK
Wu
Mei-Hwan
MH
Hsieh
Fon-Jou
FJ
D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D005312:Fetal Blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan
D017931:DNA Primers; D042965:Methylenetetrahydrofolate Reductase (NADPH2)