Genetic variants of pulmonary SP-D predict disease outcome of COPD in a Chinese population

Background and objectiveAlthough 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. MethodsA 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. ResultsWe 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). ConclusionsGenetic haplotype of SP-D may serve as a valuable prognostic indicator in Chinese patients with COPD. We demonstrated for the first time in a Chinese population cohort that genetic polymorphisms of SP-D are not only associated with risk of COPD development, but also related to disease manifestation and that they predict outcomes.