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Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population

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Abstract

Air pollution and subsequent increased oxidative stress have long been recognized as contributing factors for asthma phenotypes. Individual susceptibility to oxidative stress is determined by genetic variations of the antioxidant defence system. In this study, we analysed the association between environmental nitrogen dioxide (NO2) exposure and single nucleotide polymorphisms (SNP) in NFE2L2 and KEAP1 genes and their common impact on asthma risk. We genotyped 12 SNPs in a case–control study of 307 patients diagnosed with asthma and 344 controls. NO2 concentration was collected from the period preceding the development of asthma symptoms. Multiple logistic regression was applied to evaluate the effects of the studied genetic variations on asthma outcomes in interaction with NO2 exposure. Our data showed that genotypes of rs2588882 and rs6721961 in the regulatory regions of the NFE2L2 gene were inversely associated with infection-induced asthma (odds ratio (OR) = 0.290, p = 0.0015, and OR = 0.437, p = 0.007, respectively). Furthermore, case-only analyses revealed significant differences for these SNPs between asthma patients that lived in modestly or highly polluted environment (OR = 0.43 (0.23–0.82), p = 0.01, and OR = 0.51, p = 0.02, respectively, in a dominant model). In conclusion, our results throw some new light upon the impact of NFE2L2 polymorphisms on infection-induced asthma risk and their effect in gene–environment interactions.

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Abbreviations

AA:

Atopic asthma

HWE:

Hardy–Weinberg equilibrium

IIA:

Infection-induced asthma

NFE2L2:

Nuclear factor erythroid-derived 2-like 2

NO2 :

Nitrogen dioxide

KEAP1:

Kelch-like ECH-associated protein 1

OR:

Odds ratio

SNP:

Single nucleotide polymorphism

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Acknowledgements

We thank all the study participants for their contribution to the study. We also thank Judit Varga in the Hungarian Ministry of Rural Development for providing air quality data. This study was financially supported by OTKA (Hungarian Scientific Research Fund)—K81941 (C. Szalai) and ETT (Ministry of Health, Hungary) 415/2009 (C. Szalai)—and NKTH (National Research and Technology) TECH_08-A1/2-2008-0120 (A. Falus, C. Szalai)

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary

    Ildikó Ungvári, Éva Hadadi, Viktor Virág & András Falus

  2. Heim Pál Pediatric Hospital, PO Box 66, 1958, Budapest, Hungary

    Adrienne Nagy, András Kiss & Csaba Szalai

  3. St János Hospital, Budapest, Hungary

    Ágnes Kalmár

  4. Svábhegy National Clinic for Allergy Immmunology and Pulmonology, Budapest, Hungary

    Györgyi Zsigmond

  5. Inflammation Biology and Immunogenomics Research Group, Hungarian Academy of Sciences–Semmelweis University, Budapest, Hungary

    Ágnes F. Semsei, András Falus & Csaba Szalai

  6. Csertex Research Laboratory, Budapest, Hungary

    Csaba Szalai

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  1. Ildikó Ungvári
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  2. Éva Hadadi
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  3. Viktor Virág
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  4. Adrienne Nagy
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  7. Györgyi Zsigmond
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  8. Ágnes F. Semsei
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  9. András Falus
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  10. Csaba Szalai
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Correspondence to Csaba Szalai.

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Ungvári, I., Hadadi, É., Virág, V. et al. Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population. J Community Genet 3, 25–33 (2012). https://doi.org/10.1007/s12687-011-0075-8

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  • DOI: https://doi.org/10.1007/s12687-011-0075-8

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