Tumor necrosis factor gene complex in COPD and disseminated bronchiectasis

Cristina Patuzzo, Lucia S. Gilè, Michele Zorzetto, Elisabetta Trabetti, Giovanni Malerba, Pier Franco Pignatti, Maurizio Luisetti

Research output: Contribution to journalArticlepeer-review

Abstract

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: LtαNcoI, in the first intron of the lymphotoxin α (previously referred to as TNF-β) gene, and TNF-308, in the promoter region of the TNF-α gene. Higher levels of TNF production are associated with allele 1 of LtαNcoI (LtαNcoI*I) 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-α and LtαNcoI 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 LtαNcoI*I 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 (Δ = 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.

Original languageEnglish
Pages (from-to)1353-1358
Number of pages6
JournalChest
Volume117
Issue number5
Publication statusPublished - 2000

Keywords

  • Genetic risk factors
  • Multifactorial diseases
  • Polymerase chain reaction
  • Restriction analysis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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