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ORIGINAL RESEARCH |
From the Departments of Gynecologic Endocrinology and Reproductive Medicine, and Obstetrics and Gynecology, University of Vienna School of Medicine, Vienna, Austria, and Department of Laboratory Medicine, Hospital Kaiser Franz-Josef Spital, Vienna, Austria.
Address reprint requests to: Fritz Nagele, MD, University of Vienna School of Medicine, Department of Gynecologic Endocrinology and Reproductive Medicine, Waehringer Guertel 18-20, Vienna, A-1090, Austria; E-mail: fritz.nagele{at}akhwien.ac.at.
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 µmol/L [T/T + C/T] versus 6.5 ± 2.6 µmol/L [C/C], P = .05).
CONCLUSION: Carriage of the mutant allele of the MTHFR C677T polymorphism is associated with elevated serum levels of homocysteine and idiopathic recurrent miscarriage.
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