A single nucleotide polymorphism in a miR-1302 binding site in CGA increases the risk of idiopathic male infertility
Zhang H, Liu Y, Su D, Yang Y, Bai G, Tao D, Ma Y, Zhang S.
OBJECTIVE: To explore the possible association between single nucleotide polymorphisms (SNPs) in the miRNA-binding sites of spermatogenesis-related genes and idiopathic infertility in humans. DESIGN: Prospective study. SETTING: Research laboratory of a university hospital. PATIENT(S): A total of 494 patients with azoospermia or severe oligozoospermia and 357 fertile controls were included in our study. INTERVENTION(S): The 3' untranslated region sequences of 140 candidate genes for male infertility were analyzed using specialized algorithms including Pictar, miRanda, Targetscan, and RNAhybrid and 39 SNPs located at putative miRNA-binding sites were identified. The possible association of 6 putatively functional SNPs and male infertility was explored further with the use of case-control studies. The function of SNPs significantly associated with male infertility was analyzed by dual luciferase assay. MAIN OUTCOME MEASURE(S): Significantly associated SNPs and their influence on gene expression. RESULT(S): Two SNPs from two genes (rs6631 of CGA and rs2303846 of CPEB1) were found to be associated with idiopathic male infertility. Functionally, the substitution of A by T in rs6631 results in decreased binding affinity of miR-1302 and overexpression of CGA in vitro. CONCLUSION(S): Our results reveal for the first time that SNPs residing in miRNA-binding sites of CGA could influence expression of CGA and elevate the risk of spermatogenesis impairment. CI - Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. FAU - Zhang, Hao AU - Zhang H AD - Division of Human Morbid Genomics, State Key Laboratory of Biotherapy and Department of Medical Genetics, West China Hospital, Sichuan University, Renmin Nanlu, Chengdu, People's Republic of China. FAU - Liu, Yunqiang AU - Liu Y FAU - Su, Dan AU - Su D FAU - Yang, Yuan AU - Yang Y FAU - Bai, Gang AU - Bai G FAU - Tao, Dachang AU - Tao D FAU - Ma, Yongxin AU - Ma Y
|