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Respiratory Research

, 15:113

First Online: 21 September 2014Received: 10 June 2014Accepted: 02 September 2014


BackgroundChronic bronchitis CB is one of the classic phenotypes of COPD. The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population.

MethodsWe analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS Bergen, Norway; and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints ECLIPSE. CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years. CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry. Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls. Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis.

ResultsFor CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 rs34391416, OR = 1.93, P = 4.99 × 10 as well as significant associations of known COPD SNPs within FAM13A. In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 rs114931935, OR = 1.88, P = 4.99 × 10.

ConclusionsWe found genome-wide significant associations with CB COPD on 4q22.1 FAM13A and 11p15.5 EFCAB4A, CHID1 and AP2A2, and a locus associated with CB within COPD subjects on 1q23.3 RPL31P11 and ATF6. This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD.

Trial NCT00608764, NCT00292552

KeywordsPulmonary disease Chronic obstructive Chronic bronchitis Genome-wide association study AbbreviationsAAAfrican American

CBChronic bronchitis

ECLIPSEEvaluation of COPD longitudinally to identify predictive surrogate endpoints

GOLDGlobal initiative for chronic obstructive lung disease

GWASGenome-wide association study

NHWnon-Hispanic white

SNPSingle nucleotide polymorphism

Electronic supplementary materialThe online version of this article doi:10.1186-s12931-014-0113-2 contains supplementary material, which is available to authorized users.

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Autor: Jin Hwa Lee - Michael H Cho - Craig P Hersh - Merry-Lynn N McDonald - James D Crapo - Per S Bakke - Amund Gulsvik - A


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