Mol. Hum. Reprod. Advance Access originally published online on July 28, 2005
Molecular Human Reproduction 2005 11(7):477-480; doi:10.1093/molehr/gah204
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A polymorphism in the MTHFD1 gene increases a mother’s risk of having an unexplained second trimester pregnancy loss
1Department of Biochemistry, Trinity College Dublin, Dublin, Ireland, 2Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Institute, 3Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, Department of Health and Human Services, National Institutes of Health, Bethesda, Maryland, USA, 4Department of Clinical Medicine, Trinity College Dublin, 5Coombe Women’s Hospital and 6Child Health Epidemiology Division, Health Research Board, Dublin, Ireland
7 To whom correspondence should be addressed at: National Human Genome Research Institute, Building 50, Room 5306, 50 South Drive, MSC 8004, Bethesda, MD 20892-8004, USA. E-mail: lbrody{at}helix.nih.gov
8 Present address: Department of Obstetrics & Gynecology, University of Miami, P.O.Box 016960, Miami, FL 33101, USA
Low maternal folate or vitamin B12 status has been implicated in numerous pregnancy complications including spontaneous abortion. The primary aim of this study was to test a polymorphism within the trifunctional folate enzyme MTHFD1 (5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetase) for an association with a mother’s risk of having an unexplained second trimester pregnancy loss. We genotyped 125 women who had at least one unexplained spontaneous abortion or intrauterine fetal death between 13 and 26 weeks gestation and 625 control women with no history of prior pregnancy loss. Our study is the first to identify an association between the MTHFD1 1958G
A (R653Q) polymorphism and the maternal risk of having an unexplained second trimester pregnancy loss. Women who are MTHFD1 1958AA homozygous have a 1.64-fold increased risk of having an unexplained second trimester loss compared to women who are MTHFD1 1958AG or 1958GG [OR 1.64 (1.05–2.57), P = 0.03]. It has been reported that polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), 677CT (A222V), transcobalamin II (TCII), 776CG (P259R), are associated with pregnancy loss. Both variants were tested in this study. Neither showed evidence of significantly affecting the maternal risk of having a second trimester pregnancy loss. In conclusion, the MTHFD1 1958AA genotype may be an important maternal risk factor to consider during pregnancy.
Key words: abortion/fetal death/second trimester/spontaneous/unexplained
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