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*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.
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.
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*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 (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.