Abstract

Introduction
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with its incidence and phenotype incompletely explained by lifestyle, environmental insult or genetic predisposition. In the past, Iron Responsive Element Binding Protein 2 (IREB2) gene variants have been inconsistently associated with COPD pathogenesis. The aim of our study was to examine the association of selected IREB2 SNPs with COPD clinical phenotypes and progression.
 
Methods
A total of 165 patients with COPD, GOLD stage B-D, subjects of the HISTORIC study, a randomized, placebo-controlled, double-blind, investigator-initiated trial were enrolled in this study. Three common polymorphisms of the IREB2 gene reportedly associated with COPD pathogenesis, rs13180, rs2568494 and rs1062980 were examined in connection to clinical and functional characteristics of the patients. Genotyping was performed with real-time PCR-TAQMAN SNP Genotyping Assay.
 
Results
SNPs have been differentially associated with parameters related to lung function such as FEV1, DLCO and N2 wash out. Moreover, a significant (p<0.05) association was detected between the incidence of cough and all three IREB2 SNPs.

Conclusion
Our results indicate that there are significant associations between all three IREB2 variants examined and clinical characteristics of COPD patients. As the protein product of IREB2 is known to regulate intracellular iron homeostasis, in turn related to oxidative stress, such polymorphisms may predispose to local damage affecting airway remodeling in COPD and could conceivably be helpful in more accurate prognosis and individualized treatment of COPD.