Dataset Information

IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

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 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 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.

SUBMITTER: Lee JH

PROVIDER: S-EPMC4370263 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

Lee Jin Hwa JH Cho Michael H MH Hersh Craig P CP McDonald Merry-Lynn N ML Wells J Michael JM Dransfield Mark T MT Bowler Russell P RP Lynch David A DA Lomas David A DA Crapo James D JD Silverman Edwin K EK

American journal of respiratory cell and molecular biology 20150301 3

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 in ...[more]

PMID: 25101718

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Project description:Chronic obstructive pulmonary disease causes significant morbidity and concomitant pulmonary vascular disease and cardiac dysfunction are associated with poor prognosis. Computed tomography-detected relative pulmonary artery (PA) enlargement defined as a PA to ascending aorta diameter ratio >1 (PA:A>1) is a marker for pulmonary hypertension and predicts chronic obstructive pulmonary disease exacerbations. However, little is known about the relationship between the PA:A ratio, pulmonary blood volume, and cardiac function.A single-center prospective cohort study of patients with chronic obstructive pulmonary disease was conducted. Clinical characteristics and computed tomography metrics, including the PA:A and pulmonary blood vessel volume, were measured. Ventricular functions, volumes, and dimensions were measured by cine cardiac MRI with 3-dimensional analysis. Linear regression examined the relationships between clinical characteristics, computed tomography and cardiac MRI metrics, and 6-minute walk distance. Twenty-four patients were evaluated and those with PA:A>1 had higher right ventricular (RV) end-diastolic and end-systolic volume indices accompanied by lower RV ejection fraction (52±7% versus 60±9%; P=0.04). The PA:A correlated inversely with total intraparenchymal pulmonary blood vessel volume and the volume of distal vessels with a cross-sectional area of <5 mm(2). Lower forced expiratory volume, PA:A>1, and hyperinflation correlated with reduced RV ejection fraction. Both PA diameter and reduced RV ejection fraction were independently associated with reduced 6-minute walk distance.The loss of blood volume in distal pulmonary vessels is associated with PA enlargement on computed tomography. Cardiac MRI detects early RV dysfunction and remodeling in nonsevere chronic obstructive pulmonary disease patients with a PA:A>1. Both RV dysfunction and PA enlargement are independently associated with reduced walk distance.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00608764.

Project description:AIM:To assess the frequency of carotid artery disease (CAD) and lower extremities artery disease (LEAD) in patients with chronic obstructive pulmonary disease (COPD) and their relation to the severity of airflow limitation and the level of C-reactive protein (CRP). METHODS:We performed a cross-sectional study including 60 patients with COPD (52 male, 8 female), aged 40 to 80 years, initially diagnosed according to the actual criteria. Also, 30 subjects in whom COPD was excluded, matched to COPD patients by sex, age, body mass index and smoking status, served as controls. All study subjects completed questionnaire and underwent pulmonary evaluation (dyspnea severity assessment, baseline and post-bronchodilator spirometry, gas analyses, and chest X-ray), angiological evaluation by Doppler ultrasonography and measurement of serum CRP level. RESULTS:We found a statistically significant difference between the frequency of carotid plaques in COPD patients as compared to their frequency in controls (65% vs 30%; P = 0.002). The mean value of intima-media thickness (IMT) in COPD patients with CAD was significantly higher than its mean value in controls (0.8 ± 0.2 vs. 0.7 ± 0.2; P = 0.049). IMT value in COPD patients with CAD was significantly related to the degree of airflow limitation, i.e. to the degree of FEV1 decline (P = 0.000), as well as to the serum CRP level (P = 0.001). We found a statistically significant difference between the frequency of COPD patients with LEAD as compared to the frequency of LEAD in controls (78.3% vs 43.3%; P = 0.001). According to the Fontaine classification, COPD patients with LEAD were categorized in the stages I, IIA and IIB (53.3%, 30% and 16.7%, respectively), whereas all controls with LEAD were categorized in the Fontaine stage I. Among COPD patients with LEAD there was significant association between disease severity and clinical manifestations due to the vascular changes (P = 0.001) and serum CRP level (P = 0.001). CONCLUSION:Our findings suggest higher prevalence and higher severity of vascular changes in COPD patients as compared to their prevalence and severity in non-COPD subjects. Prevalence and severity of vascular changes in COPD patients were significantly related to the severity of airflow limitation and serum CRP levels.

Dataset Information

IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

Publications

IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

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