title: Modification of the association of bisphenol A with abnormal liver function by polymorphisms of oxidative stress-related genes.
abstract: Some studies suggested oxidative stress as a possible mechanism for the relation between exposure to bisphenol A (BPA) and liver damage. Therefore, we evaluated modification of genetic polymorphisms of cyclooxygenase 2 (COX2 or PTGS2), epoxide hydrolase 1 (EPHX1), catalase (CAT), and superoxide dismutase 2 (SOD2 or MnSOD), which are oxidative stress-related genes, on the relation between exposure to BPA and liver function in the elderly. We assessed the association of visit-to-visit variations in BPA exposure with abnormal liver function by each genotype or haplotype after controlling for age, sex, BMI, alcohol consumption, exercise, urinary cotinine levels, and low density lipoprotein cholesterol using a GLIMMIX model. A significant association of BPA with abnormal liver function was observed only in participants with COX2 GG genotype at rs5277 (odds ratio (OR)=3.04 and p=0.0231), CAT genotype at rs769218 (OR=4.16 and p=0.0356), CAT CT genotype at rs769217 (OR=4.19 and p=0.0348), SOD2 TT genotype at rs4880 (OR=2.59 and p=0.0438), or SOD2 GG genotype at rs2758331 (OR=2.57 and p=0.0457). Moreover, we also found higher OR values in participants with a pair of G-G haplotypes for COX2 (OR=2.81 and p=0.0384), G-C-A haplotype for EPHX1 (OR=4.63 and p=0.0654), A-T haplotype for CAT (OR=4.48 and p=0.0245), or T-G-A haplotype for SOD2 (OR=2.91 and p=0.0491) compared with those with the other pair of haplotypes for each gene. Furthermore, the risk score composed of 4 risky pair of haplotypes showed interactive effect with BPA on abnormal liver function (p=0.0057). Our study results suggest that genetic polymorphisms of COX2, EPHX1, CAT, and SOD2 modify the association of BPA with liver function.
authors.affiliation: Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul 151-742, Republic of Korea; Department of Bioscience and Bioengineering, Sejong University, Seoul, 05006, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: (c)Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Mee-Ri
authors.initials: MR
authors.lastname: Lee
authors.affiliation: (c)Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; (d)Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea. Electronic address: ychong1@snu.ac.kr.
authors.forename: Yun-Chul
authors.initials: YC
authors.lastname: Hong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000633:toxicity* / Q000652:urine; D002374:Catalase / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity* / Q000652:urine; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D057230:Limit of Detection; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D010636:Phenols / Q000633:toxicity* / Q000652:urine; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D013482:Superoxide Dismutase / Q000235:genetics; D000099156:Superoxide Dismutase 2; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002374:Catalase; D051546:Cyclooxygenase 2; D004785:Environmental Pollutants; D004851:Epoxide Hydrolases; D010636:Phenols; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C577219:CAT protein, human; C496540:PTGS2 protein, human; C522330:EPHX1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Genetic polymorphisms; Liver function; Oxidative stress