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HIWI and TDRD proteins are critical for piRNA biogenesis and function. Therefore, Mutations and polymorphisms in <jats:italic>HIWI<\/jats:italic> and <jats:italic>TDRD<\/jats:italic> genes may play role in male infertility. The aim of the present study was to investigate the role of <jats:italic>HIWI2<\/jats:italic> rs508485 (T&gt;C) and <jats:italic>HIWI3<\/jats:italic> rs11703684 (C&gt;T) polymorphisms and mutational analysis of TDRD5 gene in idiopathic non-obstructive azoospermia in a case-control study including 226 non-obstructive azoospermia patients and 200 fertile males. Genotyping for both polymorphisms was performed using Tetra-Primer ARMS PCR. Mutation analysis of <jats:italic>TDRD5<\/jats:italic> gene was done using multi-temperature single strand conformation polymorphism technique (MSSCP). The frequency of rs508485TC genotype was significantly different in the studied groups (P\u2009=\u20090.0032; OR\u2009=\u20092.12; 95% CI, 1.29\u20133.48). In addition, the genotype frequencies showed a significant difference under dominant model (<jats:italic>P<\/jats:italic>\u2009=\u20090.005; OR\u2009=\u20092.79; 95% CI, 1.22\u20133.13). No mutation was detected in the Tudor domain of the <jats:italic>TDRD5<\/jats:italic> in the studied patients. In conclusion, we provide evidence for association between genetic variation in the <jats:italic>HIWI2<\/jats:italic> gene and idiopathic non-obstructive azoospermia in Iranian patients. Therefore, piRNA pathway genes variants can be considered as risk factors for male infertility.<\/jats:p>","DOI":"10.1038\/s41598-017-17518-4","type":"journal-article","created":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T10:30:53Z","timestamp":1514975453000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Investigation of piwi-interacting RNA pathway genes role in idiopathic non-obstructive azoospermia"],"prefix":"10.1038","volume":"8","author":[{"given":"Zeeba","family":"Kamaliyan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Pouriamanesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsen","family":"Soosanabadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milad","family":"Gholami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1709-8975","authenticated-orcid":false,"given":"Reza","family":"Mirfakhraie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,1,9]]},"reference":[{"key":"17518_CR1","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/aja.2011.67","volume":"14","author":"A Massart","year":"2012","unstructured":"Massart, A., Lissens, W., Tournaye, H. & Stouffs, K. 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