TY - JOUR
T1 - Association of tumor necrosis factor-α-863C/A gene polymorphism with chronic obstructive pulmonary disease
AU - Chen, Yung Che
AU - Liu, Shih Feng
AU - Chin, Chien Hung
AU - Wu, Chao Chien
AU - Chen, Chung Jen
AU - Chang, Hsueh Wen
AU - Wang, Yi Hsi
AU - Chung, Yu Hsiu
AU - Chao, Tung Ying
AU - Lin, Meng Chih
PY - 2010/8
Y1 - 2010/8
N2 - The aim of this study was to investigate genetic effects on the pathogenesis of chronic obstructive pulmonary disease (COPD). The study was conducted as a prospective case-control study in a medical center in southern Taiwan. The patient group consisted of 145 male patients with smoking-related COPD and a control group of 139 resistant smokers from July 2004 to September 2009. We compared allele and genotype frequencies of three tag single nucleotide polymorphisms (SNP) of the TNF-α gene promoter region at -308, -863, and -1031 in all subjects. We also analyzed the influence of each genetic variant on pulmonary function parameters, body mass index (BMI), serum TNF-α levels, and outcomes among heavy smokers with or without COPD. COPD patients had a significantly lower A allele frequency (9.7 vs. 15.1%, OR = 0.6, p = 0.048, false discovery rate q = 0.144) and a significantly lower A carrier genotype frequency (19.3 vs. 30.2%, OR = 0.52, p = 0.042, q = 0.135) than resistant smokers. The -863 CA genotype was associated with a better FEV1/FVC ratio (79 vs. 71.5%, p = 0.034), and higher BMI (24.9 vs. 23.6 kg/m2, p = 0.048). In addition, COPD patients with the -1031 C carrier genotype had higher serum TNF-α levels (20.9 vs. 16.2 pg/ml, p = 0.01). BMI (hazard ratio = 0.84, 95% CI = 0.74-0.96, p = 0.008) was the only independent predictor for mortality. The TNF-α -863 A allele may confer a degree of resistance to the susceptibility to and muscle wasting of COPD among heavy smokers.
AB - The aim of this study was to investigate genetic effects on the pathogenesis of chronic obstructive pulmonary disease (COPD). The study was conducted as a prospective case-control study in a medical center in southern Taiwan. The patient group consisted of 145 male patients with smoking-related COPD and a control group of 139 resistant smokers from July 2004 to September 2009. We compared allele and genotype frequencies of three tag single nucleotide polymorphisms (SNP) of the TNF-α gene promoter region at -308, -863, and -1031 in all subjects. We also analyzed the influence of each genetic variant on pulmonary function parameters, body mass index (BMI), serum TNF-α levels, and outcomes among heavy smokers with or without COPD. COPD patients had a significantly lower A allele frequency (9.7 vs. 15.1%, OR = 0.6, p = 0.048, false discovery rate q = 0.144) and a significantly lower A carrier genotype frequency (19.3 vs. 30.2%, OR = 0.52, p = 0.042, q = 0.135) than resistant smokers. The -863 CA genotype was associated with a better FEV1/FVC ratio (79 vs. 71.5%, p = 0.034), and higher BMI (24.9 vs. 23.6 kg/m2, p = 0.048). In addition, COPD patients with the -1031 C carrier genotype had higher serum TNF-α levels (20.9 vs. 16.2 pg/ml, p = 0.01). BMI (hazard ratio = 0.84, 95% CI = 0.74-0.96, p = 0.008) was the only independent predictor for mortality. The TNF-α -863 A allele may confer a degree of resistance to the susceptibility to and muscle wasting of COPD among heavy smokers.
KW - COPD
KW - Genetic polymorphism
KW - Pulmonary function parameter
KW - TNF-α
UR - https://www.scopus.com/pages/publications/77955560376
U2 - 10.1007/s00408-010-9236-5
DO - 10.1007/s00408-010-9236-5
M3 - 文章
C2 - 20352242
AN - SCOPUS:77955560376
SN - 0341-2040
VL - 188
SP - 339
EP - 347
JO - Lung
JF - Lung
IS - 4
ER -