Variations in folate pathway genes are associated with unexplained female infertility

ObjectiveTo investigate associations between folate-metabolizing gene variations, folate status, and unexplained female infertility.DesignAn association study.SettingHospital-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.