A methodology to establish a database to study gene environment interactions for childhood asthma

Abstract Background A number of studies have examined the association between mold exposure and childhood asthma. However, the conclusions were inconsistent, which might be partly attributable to the lack of consideration of gene function, especially the key genes affecting the pathogenesis of childhood asthma. Research on the interactions between genes and mold exposure on childhood asthma is still very limited. We therefore examined whether there is an interaction between inflammation-related genes and mold exposure on childhood asthma. Methods A case–control study with 645 asthmatic children and 910 non-asthmatic children aged 3–12 years old was conducted. Eight single nucleotide polymorphisms (SNPs) in inflammation-related genes were genotyped using MassARRAY assay. Mold exposure was defined as self-reported visible mold on the walls. Associations between visible mold exposure, SNPs and childhood asthma were evaluated using logistic regression models. In addition, crossover analyses were used to estimate the gene-environment interactions on childhood asthma on an additive scale. Results After excluding children without information on visible mold exposure or SNPs, 608 asthmatic and 839 non-asthmatic children were included in the analyses. Visible mold exposure was reported in 151 asthmatic (24.8%) and 119 non-asthmatic children (14.2%) (aOR 2.19, 95% CI 1.62–2.97). The rs7216389 SNP in gasdermin B gene (GSDMB) increased the risk of childhood asthma with each C to T substitution in a dose-dependent pattern (additive model, aOR 1.32, 95% CI 1.11–1.57). Children carrying the rs7216389 T allele and exposed to visible mold dramatically increased the risk of childhood asthma (aOR 3.21; 95% CI 1.77–5.99). The attributable proportion due to the interaction (AP: 0.47, 95% CI 0.03–0.90) and the relative excess risk due to the interaction (RERI: 1.49, 95% CI 0–2.99) were statistically significant. Conclusions In the present study, there was a significant additive interaction between visible mold exposure and rs7216389 SNP on childhood asthma. Future studies need to consider the gene-environment interactions when exploring the risk factors of childhood asthma.

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Gene–Environment Interaction Between Interleukin-4 Promoter and Molds in Childhood Asthma

Annals of Epidemiology ◽

10.1016/j.annepidem.2012.01.008 ◽

2012 ◽

Vol 22 (4) ◽

pp. 250-256 ◽

Cited By ~ 13

Author(s):

Bing-Fang Hwang ◽

I-Ping Liu ◽

Tzu-Pi Huang

Keyword(s):

Childhood Asthma ◽

Interleukin 4 ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment

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Gene-environment interaction for childhood asthma and exposure to farming in Central Europe

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2010.09.041 ◽

2011 ◽

Vol 127 (1) ◽

pp. 138-144.e4 ◽

Cited By ~ 109

Author(s):

Markus J. Ege ◽

David P. Strachan ◽

William O.C.M. Cookson ◽

Miriam F. Moffatt ◽

Ivo Gut ◽

...

Keyword(s):

Central Europe ◽

Childhood Asthma ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment

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A Genomewide Scan For Gene-Environment Interactions Affecting Childhood Asthma

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a5687 ◽

2011 ◽

Author(s):

Cassandra E. Murcray ◽

James Baurley ◽

Frank D. Gilliland ◽

Hita Vora ◽

W. J. Gauderman

Keyword(s):

Childhood Asthma ◽

Gene Environment

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Perinatal Gene-Gene and Gene-Environment Interactions on IgE Production and Asthma Development

Clinical and Developmental Immunology ◽

10.1155/2012/270869 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Jen-Chieh Chang ◽

Lin Wang ◽

Rong-Fu Chen ◽

Chieh-An Liu

Keyword(s):

Dna Sequence ◽

Tobacco Smoke ◽

Childhood Asthma ◽

Complex Disease ◽

Current Knowledge ◽

Atopic Asthma ◽

Environmental Interactions ◽

Gene Environment ◽

Genome Wide ◽

Ige Mediated

Atopic asthma is a complex disease associated with IgE-mediated immune reactions. Numerous genome-wide studies identified more than 100 genes in 22 chromosomes associated with atopic asthma, and different genetic backgrounds in different environments could modulate susceptibility to atopic asthma. Current knowledge emphasizes the effect of tobacco smoke on the development of childhood asthma. This suggests that asthma, although heritable, is significantly affected by gene-gene and gene-environment interactions. Evidence has recently shown that molecular mechanism of a complex disease may be limited to not only DNA sequence differences, but also gene-environmental interactions for epigenetic difference. This paper reviews and summarizes how gene-gene and gene-environment interactions affect IgE production and the development of atopic asthma in prenatal and childhood stages. Based on the mechanisms responsible for perinatal gene-environment interactions on IgE production and development of asthma, we formulate several potential strategies to prevent the development of asthma in the perinatal stage.

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Faculty Opinions recommendation of Gene-environment interaction for childhood asthma and exposure to farming in Central Europe.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9748956.10437054 ◽

2011 ◽

Author(s):

Gregory Hawkins ◽

Rebecca Slager

Keyword(s):

Central Europe ◽

Childhood Asthma ◽

Environment Interaction ◽

Gene Environment Interaction ◽

Gene Environment

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The Predictive Role of Biomarkers and Genetics in Childhood Asthma Exacerbations

International Journal of Molecular Sciences ◽

10.3390/ijms22094651 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4651

Author(s):

Emanuela di Palmo ◽

Erika Cantarelli ◽

Arianna Catelli ◽

Giampaolo Ricci ◽

Marcella Gallucci ◽

...

Keyword(s):

Childhood Asthma ◽

Exhaled Breath Condensate ◽

Environment Interaction ◽

Exhaled Breath ◽

Nucleotide Polymorphisms ◽

Asthmatic Patients ◽

Asthma Exacerbations ◽

Childhood Morbidity ◽

Gene Environment

Asthma exacerbations are associated with significant childhood morbidity and mortality. Recurrent asthma attacks contribute to progressive loss of lung function and can sometimes be fatal or near-fatal, even in mild asthma. Exacerbation prevention becomes a primary target in the management of all asthmatic patients. Our work reviews current advances on exacerbation predictive factors, focusing on the role of non-invasive biomarkers and genetics in order to identify subjects at higher risk of asthma attacks. Easy-to-perform tests are necessary in children; therefore, interest has increased on samples like exhaled breath condensate, urine and saliva. The variability of biomarker levels suggests the use of seriate measurements and composite markers. Genetic predisposition to childhood asthma onset has been largely investigated. Recent studies highlighted the influence of single nucleotide polymorphisms even on exacerbation susceptibility, through involvement of both intrinsic mechanisms and gene-environment interaction. The role of molecular and genetic aspects in exacerbation prediction supports an individual-shaped approach, in which follow-up planning and therapy optimization take into account not only the severity degree, but also the risk of recurrent exacerbations. Further efforts should be made to improve and validate the application of biomarkers and genomics in clinical settings.

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