• PMID: 16861746
• Gene Name: MTRR
• Condition: Non-obstructive male infertility
• Association: Associated
• Mutation: MTHFR (C677T), MS (A2756G), MTRR (A66G)
• Population size: 685
• Population details: 685 (360 infertile patients (174 azoospermia, 186 oligoasthenoteratozoospermia (OAT)), 325 controls)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: MTHFR, MS, MTRR
• Other associated phenotypes: Non-obstructive male infertility

Association study of four polymorphisms in three folate-related enzyme genes with non-obstructive male infertility

Lee HC, Jeong YM, Lee SH, Cha KY, Song SH, Kim NK, Lee KW, Lee S.

BACKGROUND: Three typical folate metabolism enzymes-i.e. methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS) and MS reductase (MTRR) in the folate cycle-play a critical role in DNA synthesis and methylation reactions. We evaluated whether polymorphisms of these three enzymes are associated with non-obstructive male infertility. METHOD: Three hundred and sixty patients with non-obstructive infertility and 325 fertile men without any chromosomal abnormalities were included in this study. The single-nucleotide polymorphism (SNP) analysis was performed by pyrosequencing and PCR-restriction fragment length polymorphism (RFLP) analysis RESULTS: The frequencies of MTHFR 677TT and MTRR 66GG genotypes were higher in non-obstructive infertile men compared with those in fertile men. By classifying 360 infertile patients into 174 azoospermia and 186 oligoasthenoteratozoospermia (OAT) subjects, the MTHFR 677TT and MS 2756GG types were significantly associated with the azoospermia group (P = 0.0227 and 0.0063, respectively). The frequency of MTRR 66GG was significant in the OAT group (P = 0.0014 versus fertile males). CONCLUSIONS: By analysis of a large number of subjects and a more specific patient selection, we showed the first genetic evidence that MTHFR C677T, MS A2756G and MTRR A66G genotypes were independently associated with male infertility. Each SNP of the three enzymes may have a different impact on the folate cycle during spermatogenesis. FAU - Lee, Han-Chul AU - Lee HC AD - Functional Genomics Lab, CHA Research Institute, Bundang Campus, College of Medicine, Pochon CHA University, Kyunggi-Do, Republic of Korea. FAU - Jeong, Yu-Mi AU - Jeong YM FAU - Lee, Sook Hwan AU - Lee SH FAU - Cha, Kwang Yul AU - Cha KY FAU - Song, Seung-Hun AU - Song SH FAU - Kim, Nam Keun AU - Kim NK FAU - Lee, Kyo Won AU - Lee KW