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Polymorphic variation in surfactant protein B is associated with COPD exacerbations

¹ Channing Laboratory, Brigham and Women's Hospital, and Harvard Medical School, ² Pulmonary and Critical Care Division, Brigham and Women's Hospital, Boston, MA, ³ Dept of Pulmonary and Critical Care, University of Washington, Seattle, WA, and ⁴ Dept of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

CORRESPONDENCE: E. K. Silverman, Channing Laboratory, 181 Longwood Ave., Boston, MA 02115, USA, Fax: Fax: 1 6175250958. E-mail: edwin.silverman{at}channing.harvard.edu

Keywords: Association analysis, chronic obstructive pulmonary disease, exacerbations, genetics, single nucleotide polymorphisms, surfactant protein B

Received: March 15, 2008
Accepted May 28, 2008

Exacerbations of chronic obstructive pulmonary disease (COPD) reduce quality of life and increase mortality. Genetic variation might explain the substantial variability seen in exacerbation frequency among COPD subjects with similar lung function. Polymorphisms in five candidate genes, previously associated with COPD susceptibility, were analysed in order to determine whether they demonstrated association with COPD exacerbations.

A total of 88 single nucleotide polymorphisms (SNPs) in the genes microsomal epoxide hydrolase (EPHX1), transforming growth factor, beta-1 (TGFB1), serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 (SERPINE2), glutathione S-transferase pi (GSTP1) and surfactant protein B (SFTPB) were genotyped in 389 non-Hispanic white participants in the National Emphysema Treatment Trial. Exacerbations were defined as COPD-related emergency room visits or hospitalisations using the Centers for Medicare and Medicaid Services claims data.

One or more exacerbations were experienced by 216 (56%) subjects during the study period. An SFTPB promoter polymorphism, rs3024791, was associated with COPD exacerbations. Logistic regression models, analysing a binary outcome of presence or absence of exacerbations, confirmed the association of rs3024791 with COPD exacerbations. Negative binomial regression models demonstrated association of multiple SFTPB SNPs (rs2118177, rs2304566, rs1130866 and rs3024791) with exacerbation rates. Polymorphisms in EPHX1, GSTP1, TGFB1 and SERPINE2 did not demonstrate association with COPD exacerbations.

In conclusion, genetic variation in surfactant protein B is associated with chronic obstructive pulmonary disease susceptibility and exacerbation frequency.