title: Variations in folate pathway genes are associated with unexplained female infertility.
abstract: OBJECTIVE
  To investigate associations between folate-metabolizing gene variations, folate status, and unexplained female infertility.
  
  
  METHODS
  An association study.
  
  
  METHODS
  Hospital-based IVF unit and university-affiliated reproductive research laboratories.
  
  
  METHODS
  Seventy-one female patients with unexplained infertility.
  
  
  METHODS
  Blood samples for polymorphism genotyping and homocysteine, vitamin B12, and folate measurements.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility.
authors.affiliation: Department of Clinical Science, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. signe.altmae@ki.se
authors.forename: Signe
authors.initials: S
authors.lastname: Altmäe
authors.forename: Anneli
authors.initials: A
authors.lastname: Stavreus-Evers
authors.forename: Jonatan R
authors.initials: JR
authors.lastname: Ruiz
authors.forename: Margit
authors.initials: M
authors.lastname: Laanpere
authors.forename: Tiina
authors.initials: T
authors.lastname: Syvänen
authors.forename: Agneta
authors.initials: A
authors.lastname: Yngve
authors.forename: Andres
authors.initials: A
authors.lastname: Salumets
authors.forename: Torbjörn K
authors.initials: TK
authors.lastname: Nilsson