A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss

Anne Parle-McDermott, Faith Pangilinan, James L. Mills, Caroline C. Signore, Anne M. Molloy, Amanda Cotter, Mary Conley, Christopher Cox, Peadar N. Kirke, John M. Scott, Lawrence C. Brody

Research output: Contribution to journalArticlepeer-review

Abstract

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), 677C→T (A222V), transcobalamin II (TCII), 776C→G (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.

Original languageEnglish (US)
Pages (from-to)477-480
Number of pages4
JournalMolecular Human Reproduction
Volume11
Issue number7
DOIs
StatePublished - Jul 2005
Externally publishedYes

Keywords

  • Abortion
  • Fetal death
  • Second trimester
  • Spontaneous
  • Unexplained

ASJC Scopus subject areas

  • Reproductive Medicine
  • Embryology
  • Molecular Biology
  • Genetics
  • Obstetrics and Gynecology
  • Developmental Biology
  • Cell Biology

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