title: Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility.
abstract: The aim of this study was to explore the relationship between 2 genetic polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR), C677T and A1298C, and determine the long-term reproductive outcome in infertile men. This was a prospective study conducted in an andrology clinic. Men with a 1-year history of infertility were assessed for the MTHFR polymorphisms at a 5-year follow-up. We compared the MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism between men who did and did not bear children during follow-up. Of the 215 men who were infertile at 1 year, 82 (38.1%) remained infertile and 133 (61.9%) achieved natural conception during the 5-year follow-up, with the highest rate in the first year (32.6%). The MTHFR 677TT genotype (homozygote) was associated with a substantially increased risk of infertility during follow-up [odds ratio (OR) = 10.242; 95% confidence interval (CI) = 1.257-83.464] relative to the MTHFR 677CC genotype (wild-type). Risk of infertility was not increased by the MTHFR A1298C polymorphism alone, but was increased by the combination of polymorphisms MTHFR C677T and MTHFR A1298C (OR = 11.818; 95%CI = 1.415-98.674). The homozygous MTHFR C677T genotype was a risk factor for male infertility during 5-year follow-up, whereas a correlation between MTHFR A1298C and infertility was not observed. The MTHFR C677T and MTHFR A1298C polymorphisms had additive effects on male infertility.
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
authors.forename: S-S
authors.initials: SS
authors.lastname: Li
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Institute of Reproductive and Child Health, Peking University Health Science Center, Beijing, China.
authors.forename: A-G
authors.initials: AG
authors.lastname: Ren
authors.affiliation: Institute of Reproductive and Child Health, Peking University Health Science Center, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Jin
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)