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: LtalphaNcoI, 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 LtalphaNcoI (LtalphaNcoI*1) and with allele 2 of TNF-308 (TNF-308*2).


OBJECTIVE
To study the frequencies of the two TNF gene complex polymorphisms in patients with COPD and bronchiectasis.


METHODS
Association study.


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 LtalphaNcoI 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 LtalphaNcoI*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.
Patuzzo
C
C
Istituto di Biologia e Genetica, Università degli Studi di Verona Italy.
Gilè
L S
LS
Zorzetto
M
M
Trabetti
E
E
Malerba
G
G
Pignatti
P F
PF
Luisetti
M
M
D000368:Aged; D000483:Alleles; D001987:Bronchiectasis / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000175:diagnosis / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha