Journal
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Volume 44, Issue 3, Pages 316-322Publisher
AMER THORACIC SOC
DOI: 10.1165/rcmb.2009-0360OC
Keywords
COPD; surfactant protein-D; single-nucleotide polymorphisms; genetics
Funding
- National Institutes of Health [HL092601, HL007427, HL075478, HL082541, HL083069]
- Epidemiologic Research and Information Center of the United States Department of Veterans Affairs, and is a component of the Massachusetts Veterans Epidemiology Research and Information Center
- GlaxoSmithKline
- National Heart, Lung, and Blood Institute [N01HR7601, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, N01HR76119]
- Centers for Medicare and Medicaid Services
- Agency for Healthcare Research and Quality
- Medical Research Council [G0500306] Funding Source: researchfish
- MRC [G0500306] Funding Source: UKRI
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Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and abnormal inflammatory responses to noxious stimuli. Surfactant protein-D (SFTPD) is immunomodulatory and essential to host defense. We hypothesized that polymorphisms in SFTPD could influence the susceptibility to COPD. We genotyped six single-nucleotide polymorphisms (SNPs) in surfactant protein D in 389 patients with COPD in the National Emphysema Treatment Trial (NETT) and 472 smoking control subjects from the Normative Aging Study (NAS). Case-control association analysis was performed using Cochran-Armitage trend tests and multivariate logistic regression. The replication of significant associations was attempted in the Boston Early-Onset COPD Study, the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and the Bergen Cohort. We also correlated SFTPD genotypes with serum concentrations of surfactant protein-D (SP-D) in the ECLIPSE Study. In the NETT-NAS case-control analysis, four SFTPD SNPs were associated with susceptibility to COPD: rs2245121 (P = 0.01), rs911887 (P = 0.006), rs6413520 (P = 0.004), and rs721917 (P = 0.006). In the family-based analysis of the Boston Early-Onset COPD Study, rs911887 was associated with prebronchodilator and postbronchodilator FEV1 (P = 0.003 and P = 0.02, respectively). An intronic SNP in SFTPD, rs7078012, was associated with COPD in the ECLIPSE Study and the Bergen Cohort. Multiple SFTPD SNPs were associated with serum SP-D concentrations in the ECLIPSE Study. We demonstrated an association of polymorphisms in SFTPD with COPD in multiple populations. We demonstrated a correlation between SFTPD SNPs and SP-D protein concentrations. The SNPs associated with COPD and SP-D concentrations differed, suggesting distinct genetic influences on susceptibility to COPD and SP-D concentrations.
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