Zeeba Kamaliyan - Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sara Pouriamanesh - Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mona Amin-beidokhti - Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Amir Rezagholizadeh - Biology Department, Islamic Azad University, East Tehran Branch, Tehran, Iran.
Reza Mirfakhraie - Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The PIWI-interacting RNA (piRNA) pathway has an essential role in transposon silencing, meiosis progression, spermatogenesis, and germline maintenance. HIWI genes are critical for piRNA biogenesis and function. Therefore, polymorphisms in HIWI genes contribute to spermatogenesis defects and can be considered as risk factors for male infertility. The aim of the present study was to investigate the association between the HIWI۲ gene rs۵۰۸۴۸۵ polymorphism and non-obstructive azoospermia. Methods: A total of ۱۲۱ Iranian men with idiopathic azoospermia and ۱۰۰ fertile controls were genotyped for HIWI۲ rs۵۰۸۴۸۵ (T>C) polymorphism using Tetra-ARMS PCR. The presence of eight sequence-tagged site (STS) markers from the Y chromosome AZF region was also investigated by Multiplex PCR (M-PCR). Results: Thirteen (۱۰.۷۴%) patients showed Y chromosome microdeletions and therefore were excluded from the study. rs۵۰۸۴۸۵ in the ۳’UTR of HIWI۲ was associated with increased risk of azoospermia in our studied population with a P-value of ۰.۰۳۵ and odds ratio of ۲.۰۰ (CI ۹۵%: ۱.۰۴-۳.۸۶). Conclusions: We provide evidence for an association between genetic variation in the HIWI۲ gene involved in the piRNA pathway and idiopathic non-obstructive azoospermia in Iranian patients. Therefore, piRNA pathway gene variants can be considered as risk factors for male infertility.

HIWI۲, Non-obstructive azoospermia. PiRNA, Polymorphism