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

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

来源：PLos One, 2016, 11(3): e0151292.

DOI：10.1371/journal.pone.0151292

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 20q-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 preq-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 quasiq-gamma and linear regression models, respectively, with gender, body mass index and smoking habits as potential confounders. The Simes multipleq-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 pq-value = 0.00006, FDRq-corrected pq-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 pq-value = 0.0003, FDRq-corrected pq-value = 0.09). Polymorphisms in other gene regions showed a nonq-significant moderate association with STS (IL12B, TNS1) or lung 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.

• 出版日期2016-3-17