• PMID: 24737513
• Gene Name: MTHFR
• Condition: Male infertility
• Association: The MTHFR C677T and MTHFR A1298C polymorphisms had additive effects on male infertility.
• Mutation: MTHFR C677T, MTHFR A1298C
• Population size: 348
• Population details: 348 (215 men who were infertile at 1 year (82 remained infertile), 133 fertile)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility

Li SS, Li J, Xiao Z, Ren AG, Jin L.

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. FAU - Li, S-S AU - Li SS AD - Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. FAU - Li, J AU - Li J AD - Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. FAU - Xiao, Z AU - Xiao Z AD - First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Ren, A-G AU - Ren AG AD - Institute of Reproductive and Child Health, Peking University Health Science Center, Beijing, China.