Relationship between the Symptom frequency and anti-asthmatic Treatment intensity Score (STS) computed by using the weights from the GEIRD data (horizontal axis) and STS computed by using the weights from the ECRHS II data (vertical axis).

<p>Relationship between the Symptom frequency and anti-asthmatic Treatment intensity Score (STS) computed by using the weights from the GEIRD data (horizontal axis) and STS computed by using the weights from the ECRHS II data (vertical axis).</p

Main characteristics of the 520 cases of asthma identified in the GEIRD study.

<p>Main characteristics of the 520 cases of asthma identified in the GEIRD study.</p

Main characteristics of the 520 cases of asthma identified in the GEIRD study.

<p>Main characteristics of the 520 cases of asthma identified in the GEIRD study.</p

Association between the Symptom frequency and anti-asthmatic Treatment intensity Score (STS) at baseline (1991–1993) and long-term outcomes at the end of follow-up (1999–2001).

<p>Data from the ECRHS study.</p

Median of the Symptom frequency and anti-asthmatic Treatment intensity Score (STS) according to the GINA classification of asthma severity.

<p>Data from the GEIRD study.</p

Flow chart of the GEIRD study in the Pavia, Sassari, Turin and Verona centres, and selection of the cases of asthma.

<p>Flow chart of the GEIRD study in the Pavia, Sassari, Turin and Verona centres, and selection of the cases of asthma.</p

Distribution of the Symptom frequency and anti-asthmatic Treatment intensity Score (STS).

<p>Data from the GEIRD study.</p

Coding and definition of the candidate variables.

<p>Coding and definition of the candidate variables.</p

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

<div><p>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 (<a href="http://www.geird.org/" target="_blank">www.geird.org</a>), 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 <i>vs</i> 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 (r² = 0.94) in our sample, did not reach the statistical significance after adjusting for multiple testing (TC/CC <i>vs</i> 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.</p></div

Distribution of the symptom and severity score among the 326 cases of asthma included in the analysis.

<p>Distribution of the symptom and severity score among the 326 cases of asthma included in the analysis.</p