Mutation screening of the FKBP6 gene and its association study with spermatogenic impairment in idiopathic infertile men

Fkbp6 has been proved to be a new component of synaptonemal complexes and be involved in homologous chromosomes pairing and male infertility in mice. To explore the possible association between variations in the FKBP6 gene and impaired spermatogenesis in human, mutation screening of all the eight exons and the intron/exon boundaries of the gene was performed in 323 patients with azoospermia or severe oligozoospermia and 205 fertile controls by denatured HPLC and DNA sequencing. As a result, four novel and one known single nucleotide transitions were identified, including c.58-2AOG, c.111COT, c.156GOT, c.594GOA, and c.216COA (rs3750075). The frequencies of genotype CA, allele A of c.216COA and haplotype ‘GAG’ consisting of c.156GOT, c.216COA, and c.594GOA were significantly lower in infertile patients than those in controls. These findings suggest that the FKBP6 gene may play a role in modifying the susceptibility to idiopathic spermatogenic impairment in human and propose that the allele A of c.216COA seems to be a protective factor for the development of male infertility. Reproduction (2007) 133 511–516