Fertility and Sterility
Volume 94, Issue 1 , Pages 130-137, June 2010

Variations in folate pathway genes are associated with unexplained female infertility

  • Signe Altmäe, M.Sc.

      Affiliations

    • Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
    • Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
    • Corresponding Author InformationReprint requests: Signe Altmäe, M.Sc., Department of Obstetrics and Gynecology K57, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden (FAX: +46858587575).
    • ,
  • Anneli Stavreus-Evers, Ph.D.

      Affiliations

    • Department of Women's and Children's Health, Uppsala University, Akademiska Sjukhuset, Uppsala
    • ,
  • Jonatan R. Ruiz, Ph.D.

      Affiliations

    • Department of Biosciences and Nutrition, Unit for Preventive Nutrition, Karolinska Institutet, Stockholm, Sweden
    • ,
  • Margit Laanpere, M.Sc.

      Affiliations

    • Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
    • ,
  • Tiina Syvänen, M.Sc.

      Affiliations

    • Department of Women's and Children's Health, Uppsala University, Akademiska Sjukhuset, Uppsala
    • ,
  • Agneta Yngve, Ph.D.

      Affiliations

    • Department of Biosciences and Nutrition, Unit for Public Health Nutrition, Karolinska Institutet, Stockholm, Sweden
    • ,
  • Andres Salumets, Ph.D.

      Affiliations

    • Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
    • Department of Obstetrics and Gynecology, University of Tartu, Tartu, Estonia
    • ,
  • Torbjörn K. Nilsson, M.D., Ph.D.

      Affiliations

    • Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden

Received 15 December 2008; received in revised form 29 January 2009; accepted 9 February 2009. published online 26 March 2009.

Objective

To investigate associations between folate-metabolizing gene variations, folate status, and unexplained female infertility.

Design

An association study.

Setting

Hospital-based IVF unit and university-affiliated reproductive research laboratories.

Patient(s)

Seventy-one female patients with unexplained infertility.

Intervention(s)

Blood samples for polymorphism genotyping and homocysteine, vitamin B12, and folate measurements.

Main Outcome Measure(s)

Allele and genotype frequencies of the following polymorphisms: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C/T, 1298A/C, and 1793G/A, folate receptor 1 (FOLR1) 1314G/A, 1816delC, 1841G/A, and 1928C/T, transcobalamin II (TCN2) 776C/G, cystathionase (CTH) 1208G/T and solute carrier family 19, member 1 (SLC19A1) 80G/A, and concentrations of plasma homocysteine, vitamin B12, and serum folate.

Result(s)

MTHFR genotypes 677CT and 1793GA, as well as 1793 allele A were significantly more frequent among controls than in patients. The common MTHFR wild-type haplotype (677, 1298, 1793) CAG was less prevalent, whereas the rare haplotype CCA was more frequent in the general population than among infertility patients. The frequency of SLC19A1 80G/A genotypes differed significantly between controls and patients and the A allele was more common in the general population than in infertile women. Plasma homocysteine concentrations were influenced by CTH 1208G/T polymorphism among infertile women.

Conclusion(s)

Polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility.

Key Words: Female infertility, homocysteine, MTHFR, FOLR1, TCN2, CTH, SLC19A1

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 S.A. has nothing to disclose. A.S.-E. has nothing to disclose. J.R.R. has nothing to disclose. M.L. has nothing to disclose. T.S. has nothing to disclose. A.Y. has nothing to disclose. A.S. has nothing to disclose. T.K.N. has nothing to disclose.

 Supported by the European Union via the European Regional Development Fund and the Centre of Excellence in Genomics, Estonian Biocentre and Tartu University; the Estonian Ministry of Education and Science (core grants nos. 0182641s04 and PBGMR07903); the Estonian Science Foundation (grant no. 6498); the Spanish Ministry of Education (EX-2007-1124); The Swedish Research Council (2005-7293); the Swedish Society of Medicine; the Magn. Bergvalls Foundation; the Goljes Foundation; the Åke Wibergs Foundation; Nyckelfonden, Örebro; Karolinska Institutet, and the County Council of Stockholm and Örebro.

PII: S0015-0282(09)00372-0

doi:10.1016/j.fertnstert.2009.02.025

Fertility and Sterility
Volume 94, Issue 1 , Pages 130-137, June 2010

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