Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations.
OBJECTIVE
The aim of this study was determine whether the cytosine-to-thymine mutation at base 677 of the gene for methylenetetrahydrofolate reductase (C677T MTHFR ), which has been associated with neural tube defects, is also associated with congenital cardiac malformations.


METHODS
Amniotic fluid homocysteine levels were measured and the presence or absence of the C677T MTHFR mutation in amniocytes was determined in stored amniotic fluid obtained from 26 pregnancies complicated by isolated (presumed multifactorial) fetal cardiac defects and from 116 normal pregnancies.


RESULTS
The pregnancies affected by fetal cardiac defects had higher amniotic fluid homocysteine levels (1.7 +/- 1.7 vs 1.0 +/- 0.7 micromol/L; P =.07) and included more samples with homocysteine levels >90th percentile (27% vs 9%; P =.02) and more cases with the C677T MTHFR mutation (35% vs 13%; P =.01). Fifty percent of cases had either a high homocysteine level or the C677T MTHFR mutation (50% vs 20%; P =.003) and 12% had both (12% vs 0%; P =.0006).


CONCLUSIONS
Fifty percent of these isolated congenital cardiac defects were associated with either the C677T MTHFR mutation or elevated amniotic fluid homocysteine levels, or both. This finding adds to what is already known about the multiple and complex biochemical and developmental functions of the homocysteine pathway.
Wenstrom
K D
KD
Center for Research in Women's Health, Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, 35249-7333, USA.
Johanning
G L
GL
Johnston
K E
KE
DuBard
M
M
D000653:Amniotic Fluid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004587:Electrophoresis, Agar Gel; D005260:Female; D005318:Fetal Heart / Q000002:abnormalities; D006330:Heart Defects, Congenital / Q000235:genetics*; D006710:Homocysteine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011247:Pregnancy
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)