• PMID: 20940137
• Gene Name: PIWIL3/HIWI3
• Condition: Spermatogenic failure, azoospermia, oligozoospermia
• Association: Associated
• Mutation: HIWI2 (rs508485), HIWI3 non-synonymous (rs11703684)
• Population size: 958
• Population details: 958 (490 patients with idiopathic azoospermia or oligozoospermia, 468 fertile controls)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: PIWIL3/HIWI3
• Other associated phenotypes: Spermatogenic failure, azoospermia, oligozoospermia

Genetic variants in Piwi-interacting RNA pathway genes confer susceptibility to spermatogenic failure in a Chinese population

Gu A, Ji G, Shi X, Long Y, Xia Y, Song L, Wang S, Wang X.

BACKGROUND: 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. METHODS: 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. RESULTS: An SNP in the 3'untranslated 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), 1.02-2.18], and individuals with HIWI3 non-synonymous rs11703684 variant genotypes exhibited a significantly reduced oligozoospermia risk (OR = 0.70; 95% CI, 0.49-1.00). 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, 0.56-0.97). 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). CONCLUSIONS: We present the first epidemiologic evidence supporting the involvement of genetic polymorphisms in Piwi genes in spermatogenic failure. FAU - Gu, Aihua AU - Gu A AD - Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Ji, Guixiang AU - Ji G FAU - Shi, Xiangguo AU - Shi X FAU - Long, Yan AU - Long Y FAU - Xia, Yankai AU - Xia Y FAU - Song, Ling AU - Song L FAU - Wang, Shoulin AU - Wang S