Variations in folate pathway genes are associated with unexplained female infertility

Fertil Steril. 2010 Jun;94(1):130-7. doi: 10.1016/j.fertnstert.2009.02.025. Epub 2009 Mar 26.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology
  • Cross-Sectional Studies
  • Cystathionine gamma-Lyase / genetics
  • Cystathionine gamma-Lyase / physiology
  • Female
  • Folate Receptor 1
  • Folate Receptors, GPI-Anchored
  • Folic Acid / blood
  • Folic Acid / genetics*
  • Folic Acid / physiology
  • Genetic Association Studies*
  • Genetic Variation / genetics*
  • Homocysteine / blood
  • Humans
  • Infertility, Female / diagnosis*
  • Infertility, Female / enzymology
  • Infertility, Female / genetics*
  • Membrane Transport Proteins / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / physiology
  • Polymorphism, Genetic / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / physiology
  • Reduced Folate Carrier Protein
  • Signal Transduction / genetics*
  • Transcobalamins / genetics
  • Transcobalamins / physiology
  • Vitamin B 12 / blood


  • Carrier Proteins
  • FOLR1 protein, human
  • Folate Receptor 1
  • Folate Receptors, GPI-Anchored
  • Membrane Transport Proteins
  • Receptors, Cell Surface
  • Reduced Folate Carrier Protein
  • SLC19A1 protein, human
  • Transcobalamins
  • Homocysteine
  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Cystathionine gamma-Lyase
  • Vitamin B 12