Association of tumor necrosis factor-alpha-863C/A gene polymorphism with chronic obstructive pulmonary disease.
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-alpha 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-alpha 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 FEV(1)/FVC ratio (79 vs. 71.5%, p = 0.034), and higher BMI (24.9 vs. 23.6 kg/m(2), p = 0.048). In addition, COPD patients with the -1031 C carrier genotype had higher serum TNF-alpha 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-alpha -863 A allele may confer a degree of resistance to the susceptibility to and muscle wasting of COPD among heavy smokers.
Chen
Yung-Che
YC
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC. yunghechen@yahoo.com.tw
Liu
Shih-Feng
SF
Chin
Chien-Hung
CH
Wu
Chao-Chien
CC
Chen
Chung-Jen
CJ
Chang
Hsueh-Wen
HW
Wang
Yi-Hsi
YH
Chung
Yu-Hsiu
YH
Chao
Tung-Ying
TY
Lin
Meng-Chih
MC
D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009133:Muscular Atrophy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000401:mortality; D012123:Pulmonary Ventilation / Q000235:genetics / Q000502:physiology; D012907:Smoking / Q000009:adverse effects / Q000235:genetics; D013624:Taiwan; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha