Tumour necrosis factor gene complex polymorphisms 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 tumour necrosis factor (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 (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*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 LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) 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.

Associations between polymorphisms of the high-affinity immunoglobulin E receptor and late-onset airflow obstruction in older populations.

OBJECTIVES: To test the hypothesis that genetic polymorphisms in the beta subunit of the high-affinity immunoglobulin E (IgE) receptor are associated with late-onset airflow obstruction. DESIGN: Case-control candidate gene association study. SETTING: Department of Medicine for the Elderly and Respiratory Medicine in three teaching hospitals in Leicester and Manchester, United Kingdom. PARTICIPANTS: Cases with late-onset airflow obstruction with age-, sex-, and geographically matched controls. MEASUREMENTS: Subjects were genotyped for two polymorphisms of the beta subunit of the high-affinity IgE receptor (RsaI intron 2 and RsaI exon 7). The association between the polymorphisms and phenotypes was examined using contingency tables and linear regression models. RESULTS: Two hundred eighty-three cases and 144 controls were genotyped. RsaI exon 7 AA was associated with eczema (odds ratio (OR)=2.27, 95% confidence interval (CI)=1.17-4.38, P=.015). No other associations were found. Total serum IgE levels were significantly higher in cases than controls (adjusted OR for high/low IgE=2.56, 95% CI=1.53-4.28, P<.001). CONCLUSION: Serum IgE levels, but not the high-affinity IgE receptor polymorphisms, were associated with late-onset airflow obstruction, suggesting that interaction between environmental and genetic factors controlling serum IgE levels and disease pathogenesis may differ between early- and late-onset airflow obstruction phenotypes.