• PMID: 18550510
• Gene Name: CRISP2
• Condition: Male infertility
• Association: Associated
• Mutation: C196R, L59V, M176I
• Population size: 268
• Population details: 268 (92 infertile men with asthenozoo- and/or teratozoospermia, 176 control men)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: CRISP2
• Other associated phenotypes: Male infertility

Polymorphisms in the human cysteine-rich secretory protein 2 (CRISP2) gene in Australian men

Jamsai D, Reilly A, Smith SJ, Gibbs GM, Baker HW, McLachlan RI, de Kretser DM, O'Bryan MK.

BACKGROUND: Cysteine-rich secretory protein 2 (CRISP2) is localized to the human sperm acrosome and tail. It can regulate ryanodine receptors Ca(2+) gating and binds to mitogen-activated protein kinase kinase kinase 11 in the acrosome and gametogenetin 1 (GGN1) in the tail. METHODS AND RESULTS: In order to test the hypothesis that CRISP2 variations contribute to male infertility, we screened coding and flanking intronic regions in 92 infertile men with asthenozoo- and/or teratozoospermia and 176 control men using denaturing HPLC and sequencing. There were 21 polymorphisms identified, including 13 unreported variations. Three SNPs resulted in amino acid substitutions: L59V, M176I and C196R. All were only present in a heterozygous state and found in fertile men. However, the C196R polymorphism was of particular interest as it resulted in the loss of a strictly conserved cysteine involved in intramolecular disulphide bonding. Screening of an additional 637 infertile men identified 23 heterozygous C196R men to give an overall frequency of 3.6%, compared with 3.4% in control men. The functional significance of the C196R polymorphism was defined using a yeast two-hybrid assay. The C196R substitution resulted in the loss of CRISP2-GGN1 binding. CONCLUSIONS: Although none of the many polymorphisms identified herein showed a significant association with male infertility, functional studies suggested that the C196R polymorphism may compromise CRISP2 function. FAU - Jamsai, D AU - Jamsai D AD - Centre for Reproduction and Development, Monash Institute of Medical Research, Monash University, Clayton, VIC, Australia. FAU - Reilly, A AU - Reilly A FAU - Smith, S J AU - Smith SJ FAU - Gibbs, G M AU - Gibbs GM FAU - Baker, H W G AU - Baker HW FAU - McLachlan, R I AU - McLachlan RI FAU - de Kretser, D M AU - de Kretser DM