title: An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma.
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.
authors.affiliation: Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Accordini
authors.affiliation: Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Calciano
authors.affiliation: Section of Biology and Genetics, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bombieri
authors.affiliation: Section of Biology and Genetics, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malerba
authors.affiliation: Section of Biology and Genetics, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Belpinati
authors.affiliation: Section of Biology and Genetics, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Lo Presti
authors.affiliation: Section of Biology and Genetics, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Baldan
authors.affiliation: Unit of Respiratory Medicine, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Unit of Occupational Medicine, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Perbellini
authors.affiliation: Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: de Marco
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012129:Respiratory Function Tests / Q000379:methods; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D018793:Interleukin-13