Genetic Association of Surfactant Protein D with Chronic Obstructive Pulmonary Disease-related Phenotypes in Taiwan

• Main Authors: Chih-YingOu, 歐芷瑩
• Other Authors: Jiu-Yao Wang
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/54326917873299688843

碩士 === 國立成功大學 === 臨床醫學研究所 === 101 === Background: Surfactant protein D (SFTPD) results in emphysema in knockout mice and emphysema is represented in the lung of patients with chronic obstructive pulmonary disease (COPD). From observational study results, a subgroup of patients develops COPD without obvious risk factors. It highlights the potential role of genetic susceptibility to the development of COPD. We hypothesized that generic variants and serum level of SFTPD may be associated in the pathogenesis of COPD and COPD-related phenotypes among Taiwanese. Methods: A prospective, case-control and hospital-based study was designed from Jan 2003 to December 2010. In addition to quantification of SFTPD serum level, we picked up five single nucleotide polymorphisms (SNPs) of SFTPD from HapMap database for further genetic association analysis. Baseline demographic variables and degree of airflow obstruction were recorded. Frequency of exacerbation and change of lung function were assessed. Besides, inflammatory cytokines were also quantified. All-cause 3-year mortality was registered. Results: There were 320 smokers enrolled in our study (192 COPD and 128 at-risk subjects). We found that the serum level of SFTPD did significantly positive correlate with the degree of airflow obstruction and frequency of exacerbation in COPD patients. Further haplotype association analysis revealed that haplotype G-G-C-A was correlated with lower risk of COPD. When we made subgroup analysis among COPD patients, those encompassing haplotype G-G-C-A had lower SFTPD serum level, easier positive response to bronchodilator and better improvement of lung function. 3-year survival analysis showed significant difference between groups in the long-term follow up. Conclusions: Our study demonstrated the consistent results as previous investigation that the serum level of SFTPD may reflect the severity of disease. Meanwhile, the genetic variants of SFTPD had significant effect on the susceptibility and outcome of the disease.