The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study

Sally L. Chappell, Leslie Daly, Juzer Lotya, Aiman Alsaegh, Tamar Guetta-Baranes, Josep Roca, Roberto Rabinovich, Kevin Morgan, Ann B. Millar, Seamas C. Donnelly, Vera Keatings, William MacNee, Jan Stolk, Pieter S. Hiemstra, Massimo Miniati, Simonetta Monti, Clare M. O'Connor, Noor Kalsheker

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: Genetic 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 including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility.

Methods: 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.

Results: 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.

Conclusions: 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.

Original languageEnglish
Article number24
Pages (from-to)-
Number of pages7
JournalBMC Medical Genetics
Publication statusPublished - 14 Feb 2011


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