title: Oxidative Stress-Related Genetic Variants May Modify Associations of Phthalate Exposures with Asthma.
abstract: Background:Phthalate exposure may increase the risk of asthma. Little is known about whether oxidative-stress related genes may alter this association. First, this motivated us to investigate whether genetic polymorphisms of the oxidative-stress related genes glutathioneS-transferase Mu 1 (GSTM1), glutathioneS-transferase pi 1 (GSTP1), superoxide dismutase 2 (SOD2), catalase (CAT), myeloperoxidase (MPO), andEPHX1 in children are associated with phthalate urine concentrations. Second, we addressed the question whether these genes may affect the influence of phthalates on asthma.Methods:In a case-control study composed of 126 asthmatic children and 327 controls, urine phthalate metabolites (monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP) were measured by UPLC-MS/MS at age 3. Genetic variants were analyzed by TaqMan assay. Information on asthma and environmental exposures was also collected. Analyses of variance and logistic regressions were performed.Results:Urine MEHHP levels were associated with asthma (adjusted OR 1.33, 95% CI (1.11-1.60). Children with theGSTP1(rs1695) AA andSOD2(rs5746136) TT genotypes had higher MEHHP levels as compared to GG and CC types, respectively. Since onlySOD2TT genotype was significantly associated with asthma (adjusted OR (95% CI): 2.78 (1.54-5.02)), we estimated whetherSOD2variants modify the association of MEHHP levels and asthma. As MEHHP concentrations were dependent onGSTP1andSOD2, but the assessment of interaction requires independent variables, we estimated MEHHP residuals and assessed their interaction, showing that the OR forSOD2TT was further elevated to 3.32 (1.75-6.32) when the residuals of MEHHP were high.Conclusions:Urine phthalate metabolite concentrations are associated with oxidative-stress related genetic variants. Genetic variants ofSOD2, considered to be reflect oxidative stress metabolisms, might modify the association of phthalate exposure with asthma.
authors.affiliation: Department of Pediatrics, Taipei Hospital, Ministry of Health and Welfare, Taipei 11267, Taiwan. wij636@gmail.com.|Institute of Environmental & Occupational Health Sciences, School of Medicine, National Yang-Ming University, Taipei 100044, Taiwan. wij636@gmail.com.|Department of Health Risk Management, China Medical University, Taichung 110001, Taiwan. wij636@gmail.com.
authors.forename: I-Jen
authors.initials: IJ
authors.lastname: Wang
authors.affiliation: Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, Memphis, TN 38152, USA. karmaus1@memphis.edu.
authors.forename: Wilfried J J
authors.initials: WJ
authors.lastname: Karmaus
mesh_terms: D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002374:Catalase / Q000235:genetics; D002675:Child, Preschool; D004781:Environmental Exposure / Q000032:analysis; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D009195:Peroxidase / Q000235:genetics; D010795:Phthalic Acids / Q000009:adverse effects* / Q000652:urine; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000235:genetics; D053719:Tandem Mass Spectrometry; D000099156:Superoxide Dismutase 2
chemical_list: D002374:Catalase; D004851:Epoxide Hydrolases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D009195:Peroxidase; D010795:Phthalic Acids; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C479069:mono(2-ethyl-5-hydroxyhexyl) phthalate; C581825:monoethyl phthalate; C032279:phthalic acid; C522330:EPHX1 protein, human; C028577:monobutyl phthalate
keywords: GSTP1; SOD2; asthma; oxidative stress; phthalate