title: Association of tumor necrosis factor-alpha-863C/A gene polymorphism with chronic obstructive pulmonary disease.
abstract: 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.
authors.affiliation: 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
authors.forename: Yung-Che
authors.initials: YC
authors.lastname: Chen
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Liu
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chin
authors.forename: Chao-Chien
authors.initials: CC
authors.lastname: Wu
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Yi-Hsi
authors.initials: YH
authors.lastname: Wang
authors.forename: Yu-Hsiu
authors.initials: YH
authors.lastname: Chung
authors.forename: Tung-Ying
authors.initials: TY
authors.lastname: Chao
authors.forename: Meng-Chih
authors.initials: MC
authors.lastname: Lin
mesh_terms: 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*
chemical_list: D014409:Tumor Necrosis Factor-alpha