Tumor necrosis factor-alpha +489G/A gene polymorphism is associated with chronic obstructive pulmonary disease.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterized by a chronic inflammatory process, in which the pro-inflammatory cytokine Tumor Necrosis Factor (TNF)-alpha is considered to play a role. In the present study the putative involvement of TNF-alpha gene polymorphisms in pathogenesis of COPD was studied by analysis of four TNF-alpha gene polymorphisms in a Caucasian COPD population.


METHODS
TNF-alpha gene polymorphisms at positions -376G/A, -308G/A, -238G/A, and +489G/A were examined in 169 Dutch COPD patients, who had a mean forced expiratory volume in one second (FEV1) of 37 +/- 13%, and compared with a Dutch population control group of 358 subjects.


RESULTS
The data showed that the TNF-alpha +489G/A genotype frequency tended to be different in COPD patients as compared to population controls, which was due to an enhanced frequency of the GA genotype. In line herewith, carriership of the minor allele was associated with enhanced risk of development of COPD (odds ratio = 1.9, p = 0.009). The other TNF-alpha gene polymorphisms studied revealed no discrimination between patients and controls. No differences in the examined four TNF-alpha polymorphisms were found between subtypes of COPD, which were stratified for the presence of radiological emphysema. However, comparison of the COPD subtypes with controls showed a significant difference in the TNF-alpha +489G/A genotype in patients without radiological emphysema (chi2-test: p < 0.025 [Bonferroni adjusted]), while no differences between COPD patients with radiological emphysema and controls were observed.


CONCLUSIONS
Based on the reported data, it is concluded that COPD, and especially a subgroup of COPD patients without radiological emphysema, is associated with TNF-alpha +489G/A gene polymorphism.
Küçükaycan
Mehmet
M
Nutrition and Toxicology Research Institute Maastricht, Department of Pulmonology, Maastricht University, Maastricht, The Netherlands.
Van Krugten
Michiel
M
Pennings
Herman-Jan
HJ
Huizinga
Tom W J
TW
Buurman
Wim A
WA
Dentener
Mieke A
MA
Wouters
Emiel F M
EF
D000225:Adenine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005838:Genotype; D006147:Guanine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000235:genetics*; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics; D011859:Radiography; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D000225:Adenine