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Human Reproduction, Vol. 18, No. 9, 1948-1950, September 2003
© 2003 European Society of Human Reproduction and Embryology

Short Communications

Gene–gene interaction between fetal MTHFR 677C>T and transcobalamin 776C>G polymorphisms in human spontaneous abortion

Henrik Zetterberg1,4, Alexis Zafiropoulos2, Demetrios A. Spandidos2, Lars Rymo1 and Kaj Blennow1,3

1 Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, S-413 45 Göteborg, Sweden; 2 Department of Virology, Medical School, University of Crete, Heraklion, Crete, Greece and 3 Institute of Clinical Neuroscience, Department of Experimental Neuroscience, Sahlgrenska University Hospital, Göteborg University, Mölndal, Sweden

4 To whom correspondence should be addressed. e-mail: henrik.zetterberg{at}clinchem.gu.se

BACKGROUND: Genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and transcobalamin (TC) genes influence homocysteine metabolism which in turn may influence the risk of spontaneous abortion. It was hypothesized that there may be a significant interaction between MTHFR and TC genotypes which affects the pathogenesis of spontaneous abortion. METHODS AND RESULTS: A total of 76 fetal tissue samples from spontaneous abortions between weeks 6 and 20 of pregnancy, and 114 control samples from healthy blood donors were genotyped for the MTHFR 677C>T and 776C>G polymorphisms. Subjects with combined MTHFR 677TT/TC 776GG and combined MTHFR 677TT/TC 776CG genotypes gave an odds ratio for spontaneous abortion of 3.8 (95% confidence interval 1.4–9.9, P = 0.005). CONCLUSIONS: Embryos that have combined MTHFR 677TT and TC 776CG or 776GG genotypes; genotypes that individually are associated with impaired homocysteine metabolism in adults, are at increased risk for spontaneous abortion compared with embryos that have only one of these genotypes.

Key words: folate supplementation/gene linkage/gene polymorphism/homocysteine/spontaneous abortion


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