Variations in folate pathway genes are associated with unexplained female infertility.
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.
Altmäe
Signe
S
Department of Clinical Science, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. signe.altmae@ki.se
Stavreus-Evers
Anneli
A
Ruiz
Jonatan R
JR
Laanpere
Margit
M
Syvänen
Tiina
T
Yngve
Agneta
A
Salumets
Andres
A
Nilsson
Torbjörn K
TK