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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.

SUBMITTER: Accordini S

PROVIDER: S-EPMC4795623 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Accordini Simone S Calciano Lucia L Bombieri Cristina C Malerba Giovanni G Belpinati Francesca F Lo Presti Anna Rita AR Baldan Alessandro A Ferrari Marcello M Perbellini Luigi L de Marco Roberto R

PloS one 20160317 3

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 Res ...[more]

PMID: 26986948

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Project description:Asthma is characterized by episodic, reversible airflow obstruction associated with variable levels of inflammation. Over the past several decades, there has been an increasing appreciation that the clinical presentation of asthma comprises a diverse set of underlying pathologies. Rather than being viewed as a single disease entity, asthma is now thought of as a clinical syndrome with the involvement of multiple pathological mechanisms. While it is appreciated that eosinophilia is present in only a subset of patients, it remains a key feature of asthma and other eosinophilic disorders such as atopic dermatitis, eosinophilic esophagitis, and chronic rhinosinusitis with nasal polyps. Eosinophils are bone marrow-derived leukocytes present in low numbers in health; however, during disease the type 2 cytokines [interleukins (IL)-4, -5, and -13] can induce rapid eosinophilopoiesis, prolonged eosinophil survival, and trafficking to the site of injury. In diseases such as allergic asthma there is an aberrant inflammatory response leading to eosinophilia, tissue damage, and airway pathology. IL-13 is a pleiotropic type 2 cytokine that has been shown to be integral in the pathogenesis of asthma and other eosinophilic disorders. IL-13 levels are elevated in animal models of eosinophilic inflammation and in the blood and tissue of patients diagnosed with eosinophilic disorders. IL-13 signaling elicits many pathogenic mechanisms including the promotion of eosinophil survival, activation, and trafficking. Data from preclinical models and clinical trials of IL-13 inhibitors in patients have revealed mechanistic insights into the role of this cytokine in driving eosinophilia. Promising results from clinical trials further support a key mechanistic role of IL-13 in asthma and other eosinophilic disorders. Here, we provide a perspective on the role of IL-13 in asthma and other eosinophilic disorders and describe ongoing clinical trials targeting this pathway in patients with significant unmet medical needs.

Project description:BackgroundSingle nucleotide polymorphisms (SNPs) in the interleukin 13 (IL13) gene are associated with vulnerability to allergic diseases, such as asthma and allergic conjunctivitis (AC). Periostin, as an IL13-induced protein, has emerged as a novel biomarker in several allergic diseases. Data among Egyptian patients are still scarce.AimTo find out the association of IL13 rs20541 gene polymorphism and serum levels of periostin with asthma and AC among Egyptian patients.Patients and methodsEighty-one Egyptian allergic patients with asthma, AC, and both asthma and AC (27 each), were enrolled in this case-control study. Twenty-seven age and gender-matched healthy volunteers served as controls. All participants were tested for IL13 rs20541 SNP by real-time polymerase chain reaction, TaqMan method. Serum levels of periostin and IL13 were assessed by ELISA.ResultsCompared to healthy subjects, asthmatic patients had a higher frequency of the homozygous adenine/adenine (AA) genotype at IL13 rs20541 SNP (14.8% vs 3.7%) and a lower frequency of the guanosine/guanosine (GG) genotype (51.9% vs 55.6%), while AC patients had higher GG genotype (70.4% vs 55.6%) with no AA genotype detected, yet no significant difference was noticed (p = 7.053). A significantly higher serum periostin in asthmatic patients compared to controls was found (p = 0.005). Higher levels of serum periostin, although nonsignificant, were recorded in AC patients compared to controls (22.88 ± 10.01ng/mL and 17.51 ± 3.17ng/mL, respectively). Periostin was significantly higher in patients with IL13 AA and GA genotypes compared to those with GG genotype (p = 0.016). A significant positive correlation between serum periostin and serum IL13 among allergic patients was recorded (r = 0.352, p < 0.001).ConclusionAmong Egyptian patients, serum level of periostin is significantly associated with asthma and positively correlates with IL13 level supporting its utility as a diagnostic biomarker. IL13 rs20541 gene polymorphism does not seem to play an obvious role in asthma and AC, which requires further evaluation.

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

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

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