• PMID: 19583817
• Gene Name: H2BFWT
• Condition: Male infertility
• Association: Associated
• Mutation: H2BFWT (-9C > T)
• Population size: 704
• Population details: 704 (442 male infertility, 262 non-azoospermia)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: H2BFWT
• Other associated phenotypes: Male infertility

Functional polymorphism in H2BFWT-5'UTR is associated with susceptibility to male infertility

Lee J, Park HS, Kim HH, Yun YJ, Lee DR, Lee S.

H2B histone family, member W, testis-specific (H2BFWT) gene encodes a testis-specific histone that becomes incorporated into sperm chromatin. A male infertility-associated single nucleotide polymorphism (-9C > T) within the 5' untranslated region (5'UTR) of the H2BFWT gene was identified by direct sequencing. Statistical association studies showed the polymorphism significantly associated with male infertility (n = 442, P = 0.0157), especially in non-azoospermia (n = 262, P = 0.018). Furthermore, this polymorphism is also associated with sperm parameters, especially sperm count (n = 164, P = 0.0127) and vitality (n = 164, P = 0.0076). We investigated how the genetic variant at 5'UTR confers susceptibility to non-azoospermia. Western blotting of His-tag H2BFWT revealed a difference at the translational level between -9T and the wild-type -9C in the absence of change at the transcriptional level. Reporter assays showed that this reducing translational change originated from an upstream open reading frame (uORF) generated by the -9C to -9T change. Finally, in vivo H2BFWT expression in sperm was significantly dependent on the -9C > T genotype from non-azoospermia (P = 0.0061). Therefore, this polymorphism could affect the translational efficiency of a quantitatively important histone protein by the uORF. Our data implicate H2BFWT as a susceptibility factor for male infertility, possibly with other genetic and environmental factors. FAU - Lee, Jinu AU - Lee J AD - Department of Pharmacology, CHA Stem Cell Institute, School of Medicine, CHA University, Bundang-Gu, Seongnam-Si, Kyunggi-Do, Korea. FAU - Park, Hee Suk AU - Park HS FAU - Kim, Hwan Hee AU - Kim HH FAU - Yun, Yeo-Jin AU - Yun YJ FAU - Lee, Dong Ryul AU - Lee DR