Polymorphic variation in surfactant protein B is associated with COPD exacerbations

¹ Channing Laboratory, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
² Channing Laboratory, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; and Pulmonary and Critical Care Division, Brigham and Women's Hospital
³ University of Washington, Seattle, WA, USA
⁴ Pulmonary and Critical Care Division, Brigham and Women's Hospital
⁵ University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

^* To whom correspondence should be addressed. E-mail: edwin.silverman{at}channing.harvard.edu.

	Abstract

COPD exacerbations reduce quality of life and increase mortality. Genetic variation may explain the substantial variability seen in exacerbation frequency among COPD subjects with similar lung function. We analyzed whether polymorphisms in five candidate genes previously associated with COPD susceptibility also demonstrate association with COPD exacerbations.

Eighty-eight single nucleotide polymorphisms in microsomal epoxide hydrolase (EPHX1), transforming growth factor beta 1 (TGFB1), 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 hospitalizations using Centers for Medicare and Medicaid Services claims data.

216 subjects (56%) experienced one or more exacerbations during the study period. An SFTPB promoter polymorphism, rs3024791, was associated with COPD exacerbations (p=0.008). Logistic regression models analyzing a binary outcome of presence or absence of exacerbations confirmed the association of rs3024791 with COPD exacerbations (p=0.007). Negative binomial regression models demonstrated association of multiple SFTPB SNPs with exacerbation rates: rs2118177 (p=0.01), rs2304566 (p=0.002), rs1130866 (p=0.02), and rs3024791 (p=0.0007). Polymorphisms in EPHX1, GSTP1, TGFB1, and SERPINE2 did not demonstrate association with COPD exacerbations.

Variants in SFTPB are associated with COPD susceptibility and COPD exacerbation frequency.

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