title: Gene-gene and gene-environment interactions on risk of male infertility: Focus on the metabolites.
abstract: Infertility affects about 17% couples, and males contribute to half of the cases. Compared with independent effects of genetic and environmental factors, interactions between them help in the understanding of the susceptibility to male infertility. Thus, we genotyped 25 polymorphisms, measured 16 urinary chemical concentrations and explored interactions between gene-gene and gene-environment in 1039 Han Chinese using metabolomic analysis. We first observed that GSTT1 might interact with GSTM1 (Pinter=6.33×10(-8)). Furthermore, an interaction between GSTM1 and 4-n-octylphenol (4-n-OP) was identified (Pinter=7.00×10(-3)), as well as a 2-order interaction among GSTT1, GSTM1 and 4-n-OP (Pinter=0.04). Subjects with GSTT1-present and GSTM1-null genotypes were susceptible to male infertility when exposed to 4-n-OP (OR=14.05, 95% CI=4.78-60.20, P=2.34×10(-5)). Most metabolites identified were involved in the tricarboxylic acid cycle. In conclusion, it is a novel study of the interaction on male infertility from the aspect of metabolomics.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Minjian
authors.initials: M
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; State Key Laboratory of Reproductive Medicine, Wuxi Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China. Electronic address: wwu@njmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
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, Department of Andrology, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Andrology, Nanjing Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Chuncheng
authors.initials: C
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Reproductive Medicine, Wuxi Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China.
authors.forename: Lingqing
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Wuxi Maternal and Child Health Care 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 211166, China. Electronic address: shajh@njmu.edu.cn.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: xrwang@njmu.edu.cn.
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D004785:Environmental Pollutants / Q000652:urine*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007248:Infertility, Male / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D055432:Metabolomics; D016017:Odds Ratio; D010636:Phenols / Q000652:urine*; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D004785:Environmental Pollutants; D005982:Glutathione Transferase; D010636:Phenols; C474055:octylphenol; C413545:glutathione S-transferase T1
keywords: Gene-environment interaction; Gene-gene interaction; Male infertility; Metabolomics