Author:
Chappell Sally L,Daly Leslie,Lotya Juzer,Alsaegh Aiman,Guetta-Baranes Tamar,Roca Josep,Rabinovich Roberto,Morgan Kevin,Millar Ann B,Donnelly Seamas C,Keatings Vera,MacNee William,Stolk Jan,Hiemstra Pieter S,Miniati Massimo,Monti Simonetta,O'Connor Clare M,Kalsheker Noor
Abstract
AbstractBackgroundGenetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates includingIREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility.MethodsWe have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in theIREB2gene, and for four SNPs in theTGFbeta1gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre.ResultsOur data replicate the association ofIREB2SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified forTGFbeta1.ConclusionsThese studies have therefore confirmed that theIREB2locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Cited by
41 articles.
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