Altered vulnerability to asthma at various levels of ambient Benzo[a]Pyrene by CTLA4, STAT4 and CYP2E1 polymorphisms. (December 2017)

• Record Type: Journal Article
• Authors: Choi, Hyunok; Tabashidze, Nana; Rossner, Pavel; Dostal, Miroslav; Pastorkova, Anna; Kong, Sek Won; Gmuender, Hans; Sram, Radim J.
• Is Part Of: Environmental pollution. Volume 231:Part 1(2017)
• Page Start: 1134
• Page End: 1144
• Publication Date: 2017-12
• Subjects: Gene-environment interaction -- Polycyclic aromatic hydrocarbon -- Asthma -- Single nucleotide polymorphism -- Air pollution; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2017.07.057
• Languages: English
• ISSNs: 0269-7491

Abstract

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/m 3 ) 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. Graphical abstract: Highlights: High ambient B[ a ]P (6.3 to 8.5 ng/m 3 ) predict 218% higher odds of the asthma diagnosis, compared the reference range. Children's vulnerability to asthma appears to differ according to three SNPs in CTLA4, STAT4 and CYP2E1, respectively. Joint exposure to B[ a ]P as well as the identified susceptible genotypes, respectively, predict greater odds of asthma.