Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/11161
DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease
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eISSN: 1465-993X
WOS ID: 000342370600001
Scopus EID: 2-s2.0-84908157737
PMID: 25134640
Embase PUI: L600192728
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2014-08-20Document type
research articleCitation
Lee JH, Mcdonald MLN, Cho MH, Wan ES, Castaldi PJ, Hunninghake GM, et al. DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease. Respir Res. 2014 Aug 20;15:97.Abstract
Background: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD. Methods: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) < 0.7 and FEV1 < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLCCT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLCCT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis. Results: Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, beta = 0.42L, P = 4.66 x 10(-8)). Conclusions: In COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.
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https://dx.doi.org/10.1186/s12931-014-0097-yKeywords
Pulmonary diseaseChronic obstructive
Hyperinflation
Genome-wide association analysis
Total lung capacity
DNAH5
MeSH
Aged, 80 and overAged
Pulmonary Disease, Chronic Obstructive
Humans
Middle Aged
Polymorphism, Single Nucleotide
Longitudinal Studies
Total Lung Capacity
Male
Axonemal Dyneins
Female
Cohort Studies
Genome-Wide Association Study
DeCS
Estudios de CohortesPolimorfismo de Nucleótido Simple
Femenino
Capacidad Pulmonar Total
Masculino
Estudio de Asociación del Genoma Completo
Enfermedad Pulmonar Obstructiva Crónica
Estudios Longitudinales
Humanos
Persona de Mediana Edad
Anciano
Anciano de 80 o más Años
Dineínas Axonemales