Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2014 Nov;51(5):678-87.
doi: 10.1165/rcmb.2014-0135OC.

Common genetic variants associated with resting oxygenation in chronic obstructive pulmonary disease

Merry-Lynn N McDonald  1 , Michael H Cho, Inga-Cecilie Sørheim, Sharon M Lutz, Peter J Castaldi, David A Lomas, Harvey O Coxson, Lisa D Edwards, William MacNee, Jørgen Vestbo, Julie C Yates, Alvar Agusti, Peter M A Calverley, Bartolome Celli, Courtney Crim, Stephen I Rennard, Emiel F M Wouters, Per Bakke, Ruth Tal-Singer, Bruce E Miller, Amund Gulsvik, Richard Casaburi, J Michael Wells, Elizabeth A Regan, Barry J Make, John E Hokanson, Christoph Lange, James D Crapo, Terri H Beaty, Edwin K Silverman, Craig P Hersh; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints and COPDGene Investigators
Collaborators, Affiliations
Clinical Trial

Common genetic variants associated with resting oxygenation in chronic obstructive pulmonary disease

Merry-Lynn N McDonald et al. Am J Respir Cell Mol Biol. 2014 Nov.

Abstract

Hypoxemia is a major complication of chronic obstructive pulmonary disease (COPD) that correlates with disease prognosis. Identifying genetic variants associated with oxygenation may provide clues for deciphering the heterogeneity in prognosis among patients with COPD. However, previous genetic studies have been restricted to investigating COPD candidate genes for association with hypoxemia. To report results from the first genome-wide association study (GWAS) of resting oxygen saturation (as measured by pulse oximetry [Spo2]) in subjects with COPD, we performed a GWAS of Spo2 in two large, well characterized COPD populations: COPDGene, including both the non-Hispanic white (NHW) and African American (AA) groups, and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We identified several suggestive loci (P < 1 × 10(-5)) associated with Spo2 in COPDGene in the NHW (n = 2810) and ECLIPSE (n = 1758) groups, and two loci on chromosomes 14 and 15 in the AA group (n = 820) from COPDGene achieving a level of genome-wide significance (P < 5 × 10(-8)). The chromosome 14 single-nucleotide polymorphism, rs6576132, located in an intergenic region, was nominally replicated (P < 0.05) in the NHW group from COPDGene. The chromosome 15 single-nucleotide polymorphisms were rare in subjects of European ancestry, so the results could not be replicated. The chromosome 15 region contains several genes, including TICRR and KIF7, and is proximal to RHCG (Rh family C glyocoprotein gene). We have identified two loci associated with resting oxygen saturation in AA subjects with COPD, and several suggestive regions in subjects of European descent with COPD. Our study highlights the importance of investigating the genetics of complex traits in different racial groups.

Trial registration: ClinicalTrials.gov NCT00608764.

Keywords: chronic obstructive pulmonary disease; genome-wide association study; hypoxemia; oxygen saturation; pulse oximetry.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Regional association plots around single-nucleotide polymorphisms reaching genome-wide significance for association with log(SpO2) in African American subjects from COPDGene. (A) Chromosome 14; (B) chromosome 15. SpO2, oxygen saturation measured using pulse oximetry.
See this image and copyright information in PMC

References

    1. Murphy SL, Xu J, Kochanek KD.Deaths: final data for 2010. National vital statistics reports from the Centers for Disease Control and Prevention, National Center for Health Statistics Natl Vital Stat Rep 201361(4)1–118.. Available from: http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_04.pdf - PubMed
    1. Nizet TA, van den Elshout FJ, Heijdra YF, van de Ven MJ, Mulder PG, Folgering HT. Survival of chronic hypercapnic COPD patients is predicted by smoking habits, comorbidity, and hypoxemia. Chest. 2005;127:1904–1910. - PubMed
    1. Coleta KD, Silveira LV, Lima DF, Rampinelli EA, Godoy I, Godoy I. Predictors of first-year survival in patients with advanced COPD treated using long-term oxygen therapy. Respir Med. 2008;102:512–518. - PubMed
    1. Neff TA. Routine oximetry: a fifth vital sign? Chest. 1988;94:227. - PubMed
    1. Chan ED, Chan MM, Chan MM. Pulse oximetry: understanding its basic principles facilitates appreciation of its limitations. Respir Med. 2013;107:789–799. - PubMed

Publication types

MeSH terms

Associated data