Single nucleotide polymorphisms of the gonadotrophin-regulated testicular helicase (GRTH) gene may be associated with the human spermatogenesis impairment

Abstract

Background: Gonadotropin-regulated testicular RNA helicase (GRTH) is a testis-specific RNA helicase that is essential for completion of spermatogenesis and is involved in pathogenesis of impaired spermatogenesis in mouse. It is therefore reasonable to postulate that human GRTH gene may also play a role in impaired spermatogenesis in humans. To test this hypothesis, we investigated the possible association between the variations of the GRTH gene and human spermatogenesis impairment. Methods: Mutation screening of exons and intron/exon boundaries of GRTH gene was carried out by denaturing high-performance liquid chromatography (DHPLC) in 347 infertile patients with idiopathic azoospermia and severe oligozoospermia as well as 201 fertile men. Results: Four single nucleotide polymorphisms (SNP), namely IVS6+55G→T, ISV8+10A→C, c.852C→T and c.927G→A, were identified. Among them, significant differences in polymorphism frequencies were observed at the polymorphic IVS6+55G→T and c.852C→T loci between the patients and controls, and a significant association between haplotypes of these two loci and male infertility with impaired spermatogenesis was detected. Conclusions: Results of the present study indicate that SNP IVS6+55G→T and c.852C→T of GRTH gene may be associated with male infertility with azoospermia or severe oligozoospermia, suggesting that variations in GRTH gene may contribute to susceptibility to spermatogenic impairment in humans. © 2006 Oxford University Press.