title: Common SNP in hsa-miR-196a-2 increases hsa-miR-196a-5p expression and predisposes to idiopathic male infertility in Chinese Han population.
abstract: MicroRNA plays an important role in spermatogenesis. Whether pre-miRNAs polymorphisms are associated with idiopathic male infertility remains obscure. In this study, 1378 idiopathic infertile males and 486 fertile controls were included between 2006 and 2014. Genotype of three polymorphisms (hsa-mir-146a rs2910164, hsa-mir-196a-2 rs11614913, and hsa-mir-499 rs3746444) and expression of miRNA in seminal plasma were examined by TaqMan method. The role of hsa-miR-196a-5p in cell proliferation, apoptosis and cell cycle were also examined in GC-2 cells. Our results demonstrated that rs11614913 of hsa-miR-196a-2 was significantly associated with idiopathic infertility (TT vs. CT: P = 0.014; TT vs. CC: P = 0.005; TT vs. CT + CC: P = 0.003). In following stratified analysis, we found that rs11614913 exhibited a significantly higher risk of asthenospermia, oligozoospermia and azoospermia. However, no significant association was observed between the other two polymorphisms and idiopathic male infertility risk. In a genotype-expression correlation analysis, rs11614913 CC was significantly associated with elevated expression of hsa-miR-196a-5p (P < 0.05). Additionally, apoptosis levels were significantly increased in hsa-miR-196a-5p mimic treated GC-2 cells, while decreased in hsa-miR-196a-5p inhibitor treated GC-2 cells. Our data revealed a significant relationship between hsa-miR-196a-2 polymorphism and idiopathic male infertility.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Reproduction, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China.
authors.forename: Qiuqin
authors.initials: Q
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.|Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Beilei
authors.initials: B
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Epidemiology and Biostatistics, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Microbial and Molecular Systems, KULeuven, Kasteelpark Arenberg 20, B-3001 Leuven, Belgium.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Ding
authors.affiliation: Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
authors.forename: Lingqing
authors.initials: L
authors.lastname: Hu
authors.affiliation: Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
authors.forename: Daozhen
authors.initials: D
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012661:Semen / Q000378:metabolism
chemical_list: C542542:MIRN146 microRNA, human; C542543:MIRN196 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs