The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage.
OBJECTIVE
To investigate the association between the C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR), serum homocysteine levels, and idiopathic recurrent miscarriage in a Middle-European white population.


METHODS
In a case control study, we investigated 133 women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 74 healthy controls with at least two live births and no history of pregnancy loss. A DNA extraction and polymerase chain reaction followed by restriction fragment length polymorphism analysis were used to genotype women for the presence of the MTHFR C677T polymorphism. Serum homocysteine levels were assessed by a fluorescence polarization immunoassay.


RESULTS
The MTHFR allele frequencies in women with idiopathic recurrent miscarriage and controls were 34.6% and 21.6%, respectively, for the T allele (mutant) and 65.4% and 78.4%, respectively, for the C allele (wild type) (P =.007, odds ratio 1.9, 95% confidence interval 1.2, 3.1). The MTHFR genotype frequencies in women with idiopathic recurrent miscarriage and controls were: 17.3% (T/T), 34.6% (C/T), 48.1% (C/C) and 5.4% (T/T), 32.4% (C/T), 62.2% (C/C), respectively (P =.03, odds ratio 3.7, 95% confidence interval 1.2, 11.8 [T/T versus C/T and C/C]). Serum concentrations of homocysteine were significantly higher in carriers of a MTHFR mutant allele compared with women with no mutant allele (mean 7.4 +/- 2.4 micromol/L [T/T + C/T] versus 6.5 +/- 2.6 micromol/L [C/C], P =.05).


CONCLUSIONS
Carriage of the mutant allele of the MTHFR C677T polymorphism is associated with elevated serum levels of homocysteine and idiopathic recurrent miscarriage.
Unfried
Gertrud
G
Department of Gynecologic Endocrinology and Reproductive Medicine, University of Vienna School of Medicine, Vienna, Austria.
Griesmacher
Andrea
A
Weismüller
Wolfgang
W
Nagele
Fritz
F
Huber
Johannes C
JC
Tempfer
Clemens B
CB
D000026:Abortion, Habitual / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D044465:White People / Q000235:genetics
D006710:Homocysteine; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)