Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Faculty of Medicine, Semnan University of Medical Sciences, Tehran, Iran.
Sci Rep. 2018 Jan 9;8(1):142. doi: 10.1038/s41598-017-17518-4.
Genes involved in piwi-interacting RNAs (piRNAs) pathway have an essential role in spermatogenesis. HIWI and TDRD proteins are critical for piRNA biogenesis and function. Therefore, Mutations and polymorphisms in HIWI and TDRD genes may play role in male infertility. The aim of the present study was to investigate the role of HIWI2 rs508485 (T>C) and HIWI3 rs11703684 (C>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 TDRD5 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 = 0.0032; OR = 2.12; 95% CI, 1.29-3.48). In addition, the genotype frequencies showed a significant difference under dominant model (P = 0.005; OR = 2.79; 95% CI, 1.22-3.13). No mutation was detected in the Tudor domain of the TDRD5 in the studied patients. In conclusion, we provide evidence for association between genetic variation in the HIWI2 gene and idiopathic non-obstructive azoospermia in Iranian patients. Therefore, piRNA pathway genes variants can be considered as risk factors for male infertility.
与 piwi 相互作用 RNA (piRNA) 通路相关的基因在精子发生中具有重要作用。HIWI 和 TDRD 蛋白对于 piRNA 的生物发生和功能至关重要。因此，HIWI 和 TDRD 基因的突变和多态性可能在男性不育中发挥作用。本研究旨在探讨 HIWI2 基因 rs508485（T>C）和 HIWI3 基因 rs11703684（C>T）多态性以及 TDRD5 基因突变在特发性非梗阻性无精子症中的作用，采用病例对照研究，纳入 226 例非梗阻性无精子症患者和 200 例正常生育男性。采用 Tetra-Primer ARMS PCR 法对两种多态性进行基因分型。采用多温度单链构象多态性技术（MSSCP）对 TDRD5 基因突变进行分析。研究组 rs508485TC 基因型频率差异有统计学意义（P=0.0032；OR=2.12；95%CI，1.29-3.48）。此外，显性模型下基因型频率差异有统计学意义（P=0.005；OR=2.79；95%CI，1.22-3.13）。在研究患者中未检测到 TDRD5 基因 Tudor 结构域的突变。结论：我们提供了 HIWI2 基因遗传变异与伊朗特发性非梗阻性无精子症之间存在关联的证据。因此，piRNA 通路基因变异可视为男性不育的危险因素。
