title: Interactions between urinary 4-tert-octylphenol levels and metabolism enzyme gene variants on idiopathic male infertility.
abstract: Octylphenol (OP) and Trichlorophenol (TCP) act as endocrine disruptors and have effects on male reproductive function. We studied the interactions between 4-tert-Octylphenol (4-t-OP), 4-n- Octylphenol (4-n-OP), 2,3,4-Trichlorophenol (2,3,4-TCP), 2,4,5-Trichlorophenol (2,4,5-TCP) urinary exposure levels and polymorphisms in selected xenobiotic metabolism enzyme genes among 589 idiopathic male infertile patients and 396 controls in a Han-Chinese population. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to measure alkylphenols and chlorophenols in urine. Polymorphisms were genotyped using the SNPstream platform and the Taqman method. Among four phenols that were detected, we found that only exposure to 4-t-OP increased the risk of male infertility (P(trend) = 1.70×10(-7)). The strongest interaction was between 4-t-OP and rs4918758 in CYP2C9 (P(inter) = 6.05×10(-7)). It presented a significant monotonic increase in risk estimates for male infertility with increasing 4-t-OP exposure levels among men with TC/CC genotype (low level compared with non-exposed, odds ratio (OR) = 2.26, 95% confidence intervals (CI) = 1.06, 4.83; high level compared with non-exposed, OR = 9.22, 95% CI = 2.78, 30.59), but no associations observed among men with TT genotype. We also found interactions between 4-t-OP and rs4986894 in CYP2C19, and between rs1048943 in CYP1A1, on male infertile risk (P(inter) = 8.09×10(-7), P(inter) = 3.73×10(-4), respectively).We observed notable interactions between 4-t-OP exposure and metabolism enzyme gene polymorphisms on idiopathic infertility in Han-Chinese men.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Qin
authors.forename: Minjian
authors.initials: M
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Chen
authors.forename: Guizhen
authors.initials: G
authors.lastname: Du
authors.forename: Chuncheng
authors.initials: C
authors.lastname: Lu
authors.forename: John D
authors.initials: JD
authors.lastname: Meeker
authors.forename: Zuomin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000652:urine; D044466:Asian People; D016022:Case-Control Studies; D002733:Chlorophenols / Q000633:toxicity / Q000652:urine; D002853:Chromatography, Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000652:urine; D065729:Cytochrome P-450 CYP2C9; D052244:Endocrine Disruptors / Q000633:toxicity* / Q000652:urine; D005260:Female; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000201:enzymology* / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D008297:Male; D010636:Phenols / Q000633:toxicity* / Q000652:urine; D011110:Polymorphism, Genetic; D053719:Tandem Mass Spectrometry
chemical_list: D002733:Chlorophenols; D052244:Endocrine Disruptors; D010636:Phenols; C009534:2,4,5-trichlorophenol; C080417:4-octylphenol; C502485:2,3,4-trichlorophenol; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C105260:4-tert-octylphenol
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