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IREB2 and GALC Are Associated with Pulmonary Artery Enlargement in Chronic Obstructive Pulmonary Disease

Title
IREB2 and GALC Are Associated with Pulmonary Artery Enlargement in Chronic Obstructive Pulmonary Disease
Authors
Lee, Jin HwaCho, Michael H.Hersh, Craig P.McDonald, Merry-Lynn N.Wells, J. MichaelDransfield, Mark T.Bowler, Russell P.Lynch, David A.Lomas, David A.Crapo, James D.Silverman, Edwin K.COPDGene InvestigatorsECLIPSE Investigators
Ewha Authors
이진화
SCOPUS Author ID
이진화scopus
Issue Date
2015
Journal Title
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
ISSN
1044-1549JCR Link1535-4989JCR Link
Citation
vol. 52, no. 3, pp. 365 - 376
Keywords
chronic obstructive pulmonary diseasegenome-wide associationpulmonary hypertensionsubtyping
Publisher
AMER THORACIC SOC
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A <= 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 x 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P= 1.32 x 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 x 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.
DOI
10.1165/rcmb.2014-0210OC
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의학전문대학원 > 의학과 > Journal papers
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