Tumor necrosis factor gene complex in COPD and disseminated bronchiectasis

Background: Tumor necrosis factor (TNF) is a potent proinflammatory cytokine with increased levels in the sputum of COPD subjects. Two biallelic TNF gene complex polymorphisms have been described: Lt alpha NcoI, in the first intron of the lymphotoxin alpha (previously referred to as TNF-beta) gene, and TNF-308, in the promoter region of the TNF-alpha gene. Higher levels of TNF production are associated with allele 1 of Lt alpha NcoI (Lt alpha NcoI*1) and with allele 2 of TNF-308 (TNF-308*2). Study objectives: To study the frequencies of the two TNF gene complex polymorphisms in patients with COPD and bronchiectasis, Design: Association study. Subjects and methods: We studied the frequencies of these polymorphisms in 66 subjects with COPD and in 23 subjects with disseminated bronchiectasis and compared them to the frequencies in 98 healthy control subjects and 45 subjects with nonobstructive pulmonary disease. Genomic DNA samples were extracted, and TNF-alpha and Lt alpha NcoI polymorphisms were detected after polymerase chain reaction by restriction digestion. Results: We found the following frequencies: the TNF-308*2 allele was detected in 11% of COPD individuals, 15% of bronchiectasis patients, 10% of healthy control subjects, and 18% of subjects with nonobstructive pulmonary disease. The Lt alpha NcoI*1 allele was detected in 28% of COPD individuals, 30% of bronchiectasis patients, 29% of healthy control subjects, and 29% of subjects with nonobstructive pulmonary disease. We found evidence of linkage disequilibrium between the two loci (Delta = 0.068). Conclusions: We conclude that the TNF gene complex, at least in Caucasoid individuals and for the considered polymorphisms, does not seem to play a major role as genetic risk factor in COPD and bronchiectasis.