An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma

Simone Accordini; Lucia Calciano; Cristina Bombieri; Giovanni Malerba; Francesca Belpinati; Anna Rita Lo Presti; Alessandro Baldan; Marcello Ferrari; Luigi Perbellini; Roberto de Marco

doi:10.1371/journal.pone.0151292

An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma

PLoS One. 2016 Mar 17;11(3):e0151292. doi: 10.1371/journal.pone.0151292. eCollection 2016.

Affiliations

¹ Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
² Section of Biology and Genetics, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
³ Unit of Respiratory Medicine, Department of Medicine, University of Verona, Verona, Italy.
⁴ Unit of Occupational Medicine, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.

Abstract

Different genes are associated with categorical classifications of asthma severity. However, continuous outcomes should be used to catch the heterogeneity of asthma phenotypes and to increase the power in association studies. Accordingly, the aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) in candidate gene regions and continuous measures of asthma severity, in adult patients from the general population. In the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (www.geird.org), 326 subjects (aged 20-64) with ever asthma were identified from the general population in Verona (Italy) between 2007 and 2010. A panel of 236 SNPs tagging 51 candidate gene regions (including one or more genes) was analysed. A symptom and treatment score (STS) and pre-bronchodilator FEV1% predicted were used as continuous measures of asthma severity. The association of each SNP with STS and FEV1% predicted was tested by fitting quasi-gamma and linear regression models, respectively, with gender, body mass index and smoking habits as potential confounders. The Simes multiple-test procedure was used for controlling the false discovery rate (FDR). SNP rs848 in the IL13 gene region (IL5/RAD50/IL13/IL4) was associated with STS (TG/GG vs TT genotype: uncorrected p-value = 0.00006, FDR-corrected p-value = 0.04), whereas rs20541 in the same gene region, in linkage disequilibrium with rs848 (r(2) = 0.94) in our sample, did not reach the statistical significance after adjusting for multiple testing (TC/CC vs TT: uncorrected p-value = 0.0003, FDR-corrected p-value = 0.09). Polymorphisms in other gene regions showed a non-significant moderate association with STS (IL12B, TNS1) or lung function (SERPINE2, GATA3, IL5, NPNT, FAM13A) only. After adjusting for multiple testing and potential confounders, SNP rs848 in the IL13 gene region is significantly associated with a continuous measure of symptom severity in adult subjects with ever asthma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Asthma / genetics*
Asthma / pathology
Asthma / physiopathology
Female
Gene Frequency
Genetic Predisposition to Disease / genetics*
Genotype
Humans
Interleukin-13 / genetics*
Linkage Disequilibrium
Male
Middle Aged
Polymorphism, Single Nucleotide*
Respiratory Function Tests / methods
Severity of Illness Index
Young Adult

Substances

Interleukin-13

Grants and funding

The GEIRD project was funded by the Cariverona Foundation (Bando 2006), the Italian Ministry of Health (RF-2009-1471235), Chiesi Farmaceutici and the Italian Medicines Agency (AIFA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.