Genetic variants in Piwi-interacting RNA pathway genes confer susceptibility to spermatogenic failure in a Chinese population
Authors: Gu, Aihua; Ji, Guixiang; Shi, Xiangguo; Long, Yan; Xia, Yankai; Song, Ling; Wang, Shoulin; Wang, Xinru
Source: Human Reproduction, Volume 25, Number 12, 11 December 2010 , pp. 2955-2961(7)
Publisher: Oxford University Press
The Piwi subfamily of genes is involved in spermatogenesis for the maintenance and meiosis of germline stem cells. Mice bearing targeted mutations in Piwi genes (Miwi, Mili and Miwi2) are sterile with distinct defects in spermatogenesis. We hypothesized that Piwi gene polymorphisms could be a risk factor for spermatogenic failure.
For this study, 490 patients with idiopathic azoospermia or oligozoospermia and 468 fertile controls were recruited from an infertility clinic. Nine single nucleotide polymorphisms (SNPs) of four Piwi genes (PIWIL1/HIWI, PIWIL2/HILI, PIWIL3/HIWI3 and PIWIL4/HIWI2) were genotyped using the SNPstream 12-plex platform and the Taqman method.
An SNP in the 3untranslated region of HIWI2 and a non-synonymous SNP in HIWI3 were significantly associated with an altered risk of oligozoospermia. The variant-containing genotypes of HIWI2 rs508485 exhibited a significantly increased risk, with an odds ratios (OR) of 1.49 [95 confidence interval (CI), 1.022.18], and individuals with HIWI3 non-synonymous rs11703684 variant genotypes exhibited a significantly reduced oligozoospermia risk (OR 0.70; 95 CI, 0.491.00). The haplotype analysis showed that a common haplotype of HIWI2 was associated with a significant reduction in the risk of oligozoospermia (OR 0.73, 95 CI, 0.560.97). In addition, to assess the cumulative effects, we performed a combined unfavourable genotype analysis. A significant trend towards increased risk of oligozoospermia with an increasing number of unfavourable genotypes was observed (P for trend < 0.001).
We present the first epidemiologic evidence supporting the involvement of genetic polymorphisms in Piwi genes in spermatogenic failure.
Document Type: Research Article
Publication date: 11 December 2010
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.