Tumour necrosis factor gene complex polymorphisms and haplotypes in chronic obstructive pulmonary disease

We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher TNF secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTα) polymorphisms was carried out by ‘blinded’ laboratory staff. 361 individuals (220 cases and 141 controls) were recruited. We showed an association between the LTαNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTαNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTαNcol*2 allele possessed (for FVC, regression coefficient (95% CI) = -3.73 (-7.01to -0.44), p=0.026; for FEV1 regression coefficient = -3.56 (-7.80 to 0.70), p = 0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.