Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/20006
Título
DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease
Autor(es)
Lee, Jin Hwa | McDonald, Merry-Lynn N. | Cho, Michael H. | Wan, Emily S. | Castaldi, Peter J. | Hunninghake, Gary M. | Marchetti, Nathaniel | Lynch, David A. | Crapo, James D. | Lomas, David A. | Coxson, Harvey O. | Bakke, Per S. | Silverman, Edwin K. | Hersh, Craig P | COPDGene & ECLIPSE Investigators
Fecha de publicación
2014-08-20
Cita
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.
Idioma
Inglés
Tipo de documento
research article
Resumen
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.
Palabras clave
Pulmonary disease | Chronic obstructive | Hyperinflation | Genome-wide association analysis | Total lung capacity | DNAH5
MESH
Aged, 80 and over | Aged | 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 Cohortes | Polimorfismo 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
Versión en línea
DOI
Aparece en las colecciones
Acceso a texto completo