Hyunok Choi1, Nana Tabashidze2, Pavel Rossner3, Miroslav Dostal4, Anna Pastorkova5, Sek Won Kong6, Hans Gmuender7, Radim J Sram8. 1. Departments of Environmental Health Sciences, Epidemiology, and Biostatistics University at Albany School of Public Health, One University Place, Room 153, Rensselaer, NY 12144-3456, USA. Electronic address: hchoi@albany.edu. 2. Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic. Electronic address: nanatabashidze@yahoo.com. 3. Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic. Electronic address: prossner@biomed.cas.cz. 4. Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic. Electronic address: dostal@biomed.cas.cz. 5. Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic. 6. Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA. Electronic address: sekwon.kong@childrens.harvard.edu. 7. Genedata AG, Margarethenstrasse 38, CH-4053, Basel, Switzerland. Electronic address: hans.gmuender@genedata.com. 8. Department of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, v.v.i., Vídeňská 1083, 142 20, Prague 4, Czech Republic. Electronic address: sram@biomed.cas.cz.
Abstract
BACKGROUND: Within fossil- and solid-fuel dependent geographic locations, mechanisms of air pollution-induced asthma remains unknown. In particular, sources of greater genetic susceptibility to airborne carcinogen, namely, benzo[a]pyrene (B[a]P) has never been investigated beyond that of a few well known genes. OBJECTIVES: To deepen our understanding on how the genotypic variations within the candidate genes contribute to the variability in the children's susceptibility to ambient B[a]P on doctor-diagnosed asthma. METHODS: Clinically confirmed asthmatic versus healthy control children (aged, 7-15) were enrolled from historically polluted and rural background regions in Czech Republic. Contemporaneous ambient B[a]P concentration was obtained from the routine monitoring network. The sputum DNA was genotyped for 95 genes. B[a]P interaction with SNPs was studied by two-stage, semi-agnostic screening of 621 SNPs. RESULTS: The median B[a]P within the highly polluted urban center was 8-times higher than that in the background region (7.8 vs. 1.1 ng/m3) during the period of investigation. Within the baseline model, which considered B[a]P exposure-only, the second tertile range was associated with a significantly reduced odds (aOR = 0.28) of asthma (95% CI, 0.16 to 0.50) compared to those at the lowest range. However, the highest range of B[a]P was associated with 3.18-times greater odds of the outcome (95% CI, 1.77 to 5.71). Within the gene-environment interaction models, joint occurrence of a high B[a]P exposure range and having a high-risk genotype at CTLA4 gene (rs11571316) was associated with 9-times greater odds (95% CI, 4.56-18.36) of the asthma diagnosis. Similarly, rs11571319 at CTLA4 and a high B[a]P exposure range was associated with a 8-times greater odds (95% CI, 3.95-14.27) of asthma diagnosis. Furthermore, having TG + GG genotypes on rs1031509 near STAT4 was associated with 5-times (95% CI, 3.03-8.55) greater odds of asthma diagnosis at the highest B[a]P range, compared to the odds at the reference range. Also CYP2E1 AT + TT genotypes (rs2070673) was associated with 5-times (95% CI, 3.1-8.8) greater odds of asthma diagnosis at the highest B[a]P exposure. CONCLUSIONS: The children, who jointly experience a high B[a]P exposure (6.3-8.5 ng/m3) as well as susceptible genotypes in CTLA4 (rs11571316 and rs11571319), STAT4 (rs1031509), and CYP2E1 (rs2070673), respectively, are associated with a significantly greater odds of having doctor-diagnosed asthma, compared to those with neither risk factors.
BACKGROUND: Within fossil- and solid-fuel dependent geographic locations, mechanisms of air pollution-induced asthma remains unknown. In particular, sources of greater genetic susceptibility to airborne carcinogen, namely, benzo[a]pyrene (B[a]P) has never been investigated beyond that of a few well known genes. OBJECTIVES: To deepen our understanding on how the genotypic variations within the candidate genes contribute to the variability in the children's susceptibility to ambient B[a]P on doctor-diagnosed asthma. METHODS: Clinically confirmed asthmatic versus healthy control children (aged, 7-15) were enrolled from historically polluted and rural background regions in Czech Republic. Contemporaneous ambient B[a]P concentration was obtained from the routine monitoring network. The sputum DNA was genotyped for 95 genes. B[a]P interaction with SNPs was studied by two-stage, semi-agnostic screening of 621 SNPs. RESULTS: The median B[a]P within the highly polluted urban center was 8-times higher than that in the background region (7.8 vs. 1.1 ng/m3) during the period of investigation. Within the baseline model, which considered B[a]P exposure-only, the second tertile range was associated with a significantly reduced odds (aOR = 0.28) of asthma (95% CI, 0.16 to 0.50) compared to those at the lowest range. However, the highest range of B[a]P was associated with 3.18-times greater odds of the outcome (95% CI, 1.77 to 5.71). Within the gene-environment interaction models, joint occurrence of a high B[a]P exposure range and having a high-risk genotype at CTLA4 gene (rs11571316) was associated with 9-times greater odds (95% CI, 4.56-18.36) of the asthma diagnosis. Similarly, rs11571319 at CTLA4 and a high B[a]P exposure range was associated with a 8-times greater odds (95% CI, 3.95-14.27) of asthma diagnosis. Furthermore, having TG + GG genotypes on rs1031509 near STAT4 was associated with 5-times (95% CI, 3.03-8.55) greater odds of asthma diagnosis at the highest B[a]P range, compared to the odds at the reference range. Also CYP2E1 AT + TT genotypes (rs2070673) was associated with 5-times (95% CI, 3.1-8.8) greater odds of asthma diagnosis at the highest B[a]P exposure. CONCLUSIONS: The children, who jointly experience a high B[a]P exposure (6.3-8.5 ng/m3) as well as susceptible genotypes in CTLA4 (rs11571316 and rs11571319), STAT4 (rs1031509), and CYP2E1 (rs2070673), respectively, are associated with a significantly greater odds of having doctor-diagnosed asthma, compared to those with neither risk factors.
Authors: Daniel Fernández; Radim J Sram; Miroslav Dostal; Anna Pastorkova; Hans Gmuender; Hyunok Choi Journal: Int J Environ Res Public Health Date: 2018-01-10 Impact factor: 3.390
Authors: Giovanna Cilluffo; Giuliana Ferrante; Nicola Murgia; Rosanna Mancini; Simona Pichini; Giuseppe Cuffari; Vittoria Giudice; Nicolò Tirone; Velia Malizia; Laura Montalbano; Salvatore Fasola; Roberta Pacifici; Giovanni Viegi; Stefania La Grutta Journal: Int J Environ Res Public Health Date: 2022-02-05 Impact factor: 3.390