Association of IL-1 beta and IL-1 receptor antagonist haplotypes with rateof decline in lung function in smokers

Background-There is increasing evidence that the cytokine network is centra l to the immunopathology of inflammatory airway diseases. The interleukin 1 (IL-1) receptor antagonist (IL-1RN) is a naturally occurring anti-inflamma tory agent that binds to the IL-1 receptor but does not possess agonist act ivity. Each of the genes of the IL-1 locus on chromosome 2q14 is polymorphi c. The IL1RN gene contains an 86 bp tandem repeat and allele 2 of this poly morphism has been associated with various inflammatory diseases. The IL-1 b eta (IL1B) gene contains a promoter polymorphism (C-511T) that has been ass ociated with inflammatory diseases and is in linkage disequilibrium with th e IL1RN polymorphism. Methods-We investigated whether polymorphisms in the IL1B and IL1RN genes w ere associated with rate of decline of lung function. Genotypes were determ ined in 284 smokers with a rapid decline in lung function and 306 smokers w ith no decline in lung function. Results-None of the genotypes was associated with the rate of decline of lu ng function. However, the distribution of IL1B/IL1RN haplotypes was differe nt between smokers with a rapid decline in lung function and those with no decline in lung function (p=0.0005). Conclusion-These results suggest that IL1B/IL1RN haplotypes play a role in the rate of decline in lung function in smokers.