DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

Autor: Marilyn Foreman, Arkadiusz Sitek, Marc Willis, L. Alexandre Frigini, Emily Wan, John Newell, Jørgen Vestbo, Raul San Jose Estepar, Jin Hwa Lee, Gregory Kinney, Yuriy Feshchenko, Frank Sciurba, Eric Hoffman, Mitja Košnik, Robert Wise, Jeffrey Curtis, Merry-Lynn McDonald
Rok vydání: 2014
Předmět:
Male
Vital capacity
humanos
Genome-wide association study
Pulmonary function testing
Cohort Studies
Pulmonary Disease
Chronic Obstructive
0302 clinical medicine
Lung volumes
Longitudinal Studies
estudios de cohortes
mediana edad
Aged
80 and over
anciano
0303 health sciences
COPD
medicine.diagnostic_test
Middle Aged
capacidad pulmonar total
3. Good health
Cardiology
Female
medicine.symptom
dineínas del axonema
Pulmonary and Respiratory Medicine
Spirometry
medicine.medical_specialty
Hyperinflation
Air trapping
Polymorphism
Single Nucleotide
Chronic obstructive
03 medical and health sciences
FEV1/FVC ratio
Internal medicine
medicine
Humans
Genome-wide association analysis
Aged
030304 developmental biology
business.industry
Research
Total Lung Capacity
Axonemal Dyneins
DNAH5
medicine.disease
Total lung capacity
respiratory tract diseases
Surgery
030228 respiratory system
estudio de asociación genómica completa
estudios longitudinales
Pulmonary disease
business
Genome-Wide Association Study
Zdroj: Lee, J H, McDonald, M-L N, Cho, M H, Wan, E S, Castaldi, P J, Hunninghake, G M, Marchetti, N, Lynch, D A, Crapo, J D, Lomas, D A, Coxson, H O, Bakke, P S, Silverman, E K, Hersh, C P, COPDGene and ECLIPSE Investigators & Mattheisen, M 2014, ' DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease ' Respiratory Research Review, vol. 15, pp. 97 . https://doi.org/10.1186/s12931-014-0097-y
Respiratory Research
ISSN: 1465-993X
DOI: 10.1186/s12931-014-0097-y
Popis: 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.
This work was supported by NIH R01 HL094635 (C. P. H.), R01 NR013377 (C. P. H.), R01 HL089856 (E. K. S.), P01 HL105339 (E. K. S.), and R01HL089897 (J.D.C.) The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Siemens, GlaxoSmithKline, and Sunovion. The Norway GenKOLS study (Genetics of Chronic Obstructive Lung Disease, GSK code RES11080) and the ECLIPSE study (NCT00292552; GSK code SCO104960) were sponsored by GlaxoSmithKline.
Databáze: OpenAIRE
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