Genetic variants of pulmonary SP-D predict disease outcome of COPD in a Chinese population.
OBJECTIVE
Although surfactant protein-D (SP-D) has been suggested as a biomarker for chronic obstructive pulmonary disease (COPD), the relationship between genetic variants of SP-D and disease outcome of COPD remains unknown. We hypothesized that genetic polymorphisms of SP-D are associated with COPD-related phenotypes and disease prognosis.


METHODS
A hospital-based, case-controlled study was conducted prospectively. Six single nucleotide polymorphisms of the SFTPD gene were determined for genetic association analysis. Inflammatory cytokines and SP-D serum level were quantified. Frequency of exacerbation and change of lung function were assessed. All-cause 3-year mortality was registered.


RESULTS
We studied 320 smokers (192 with COPD and 128 at-risk for COPD) who were prospectively monitored for at least 3 years. The serum levels of SP-D in COPD patients were significantly associated with the degree of airflow obstruction and frequency of exacerbation. Haplotype association analysis revealed that haplotype G-G-C-C-A was associated with lower risk of COPD (P = 0.03) in our study population. COPD patients with haplotype G-G-C-C-A had lower serum SP-D levels (P < 0.001), higher rates of positive response to bronchodilator treatment (P = 0.01), more improvement of forced expiratory volume in 1 s in yearly follow-up (P = 0.03) and better 3-year survival rate than COPD patients with non G-G-C-C-A haplotype (P = 0.03).


CONCLUSIONS
Genetic haplotype of SP-D may serve as a valuable prognostic indicator in Chinese patients with COPD.
Division of Chest Medicine, Department of Internal Medicine.
Chih-Ying
CY
Ou
Chiung-Zuei
CZ
Chen
Tzuen-Ren
TR
Hsiue
Sheng-Hsiang
SH
Lin
Jiu-Yao
JY
Wang
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001993:Bronchodilator Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D002681:China; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood / Q000235:genetics*; D015996:Survival Rate
D015415:Biomarkers; D001993:Bronchodilator Agents; D037663:Pulmonary Surfactant-Associated Protein D
chronic obstructive pulmonary disease; haplotype; polymorphism; surfactant protein D