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Polymorphisms in Surfactant Protein–D Are Associated with Chronic Obstructive Pulmonary Disease
- Source :
- American Journal of Respiratory Cell and Molecular Biology. 44:316-322
- Publication Year :
- 2011
- Publisher :
- American Thoracic Society, 2011.
-
Abstract
- 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 FEV(1) (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.
- Subjects :
- Male
Pulmonary and Respiratory Medicine
Aging
medicine.medical_specialty
Pathology
Chronic bronchitis
Genotype
Clinical Biochemistry
Population
Single-nucleotide polymorphism
Polymorphism, Single Nucleotide
Gastroenterology
Cohort Studies
Pulmonary Disease, Chronic Obstructive
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
Longitudinal Studies
Prospective Studies
education
Prospective cohort study
Molecular Biology
Aged
Inflammation
education.field_of_study
COPD
Polymorphism, Genetic
business.industry
Case-control study
Surfactant protein D
Articles
Cell Biology
Middle Aged
Pulmonary Surfactant-Associated Protein D
medicine.disease
respiratory tract diseases
Case-Control Studies
Female
business
Cohort study
Subjects
Details
- ISSN :
- 15354989 and 10441549
- Volume :
- 44
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory Cell and Molecular Biology
- Accession number :
- edsair.doi.dedup.....03450a0905c014e9171c6c6febdef05e