%0 Journal Article
%T The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study
%A Sally L Chappell
%A Leslie Daly
%A Juzer Lotya
%A Aiman Alsaegh
%A Tamar Guetta-Baranes
%A Josep Roca
%A Roberto Rabinovich
%A Kevin Morgan
%A Ann B Millar
%A Seamas C Donnelly
%A Vera Keatings
%A William MacNee
%A Jan Stolk
%A Pieter S Hiemstra
%A Massimo Miniati
%A Simonetta Monti
%A Clare M O'Connor
%A Noor Kalsheker
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-24
%X We 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 the IREB2 gene, and for four SNPs in the TGFbeta1 gene. 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.Our data replicate the association of IREB2 SNPs 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 for TGFbeta1.These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, and is predicted to become the 4th leading cause of death by the year 2030 [1]. Whilst smoking is a significant environmental cause of COPD, not all smokers will develop disease. It is well recognised that COPD has a genetic component as well as environmental, and that this may account for these differences in susceptibility.Many candidate gene studies have been carried out over the past few years, with varying degrees of reproducibility. Conflicting results may be due to population differences, spurious results caused by small sample sizes and the subsequent low power of the study to detect true associations or to variation in the phenotype. Meta-analysis can be used to pool results from genetic studies and give an overall conclusion, and this approach has been used to summarise the results for several COPD candidates [2]. This study revealed significant associations for three polymorphisms in transforming growth factor beta 1 (TGFB1), although it was acknowledged that this was a limited analy
%U http://www.biomedcentral.com/1471-2350/12/24