Mutational Analysis Of FKBP6 Gene In Patients With Idiopathic Azoospermia

Approximately 10-15% of couples are infertile, and about half of such cases are due to male factor. The male infertility with unknown etiology is nominated as idiopathic male infertility and is frequently accompanied with azoospermia or severe oligospermia. Extensive researches have confirmed that many such cases have their genetic backgrounds. Futhermore studies on over 200 infertile mouse genetic models, have discovered increasing munber of azoospermia-releted genes, suggesting that their human homologues probably also play an essential role in the etiology of human idiopathic azoospermia and oligospermia.Synaptonemal complex (SC) is a meiosis-specific supramolecular proteinaceous structure at meiosis I. Synaptonemal complex proteins (SCPs) includes SCP1, SCP2, SCP3 and it is known that null mutation of Scp3 in mice resulted in azoospermia and infertility. In human male patients with non-obstructive infertility the loss of single nucleotide of SCP3 also led to azoospermia by mutational analysis, recently, abnormalities of SCP1 in azoospermia patients had been detected and the investigations and mutational analysis of SCP1 gene are under way.Besides SCP genes, another interesting mice gene Fkbp6 has been considered as a component of SC. It has been found that exon 8 or full deletion of Fkbp6 in male mice resulted in azoospermia and infertility suggesting that its human homologue FKBP6 also is associated with humanidiopathic azoospermia. So, it is necessary to study the FKBP6 gene more deeply.To investigate the potential role of FKBP6 gene in human with idiopathic azoospermia, we perform mutational screening and polymorphic analysis of all 8 exons of FKBP6 in Chinese including 177 patients with idiopathic azoospermia and 231 healthy fertile men as control using PCR, DHPLC (Denaturing High-Performance Liquid Chromatography), RFLP (Restricted Fragment Length Polymorphism), DNA sequencing and other molecular cloning techniques. The results are as follows:Neither entire nor partial deletion was detected in any exons of FBKP6 gene in patients with idiopathic azoospermia or control. However the allele frequencies of a cSNP, namely 278C/A (rs3750075) in exon3 have been found significantly different between case and control groups. The frequency of CA genotype and 278A allele was significantly higher in controls than that in patients (by genotype tf=4. 319, P=0. 038; by allelex2=4. 156, P=0. 041). In addition, we discovered a novel cSNP~656G/A in exon6, which results in replacement of CTG for CTA, but no obvious difference in allele or genotype was found between case and control groups.