Association of IL-1β and IL-1 receptor antagonist haplotypes with rate of decline in lung function in smokers
- aUBC McDonald Research Laboratories/iCAPTURE Center, St Paul's Hospital, Vancouver, BC, Canada V6Z 1Y6, bDivision of Biostatistics, School of Public Health, University of Minnesota, USA, cFaculty of Medicine, University of Manitoba, Canada
- Dr A J Sandford
- Received 6 September 2000
- Revision requested 8 November 2000
- Revised 31 May 2001
- Accepted 18 June 2001
BACKGROUND There is increasing evidence that the cytokine network is central to the immunopathology of inflammatory airway diseases. The interleukin 1 (IL-1) receptor antagonist (IL-1RN) is a naturally occurring anti-inflammatory agent that binds to the IL-1 receptor but does not possess agonist activity. Each of the genes of the IL-1 locus on chromosome 2q14 is polymorphic. The IL1RNgene contains an 86 bp tandem repeat and allele 2 of this polymorphism has been associated with various inflammatory diseases. The IL-1β (IL1B) gene contains a promoter polymorphism (C-511T) that has been associated with inflammatory diseases and is in linkage disequilibrium with the IL1RNpolymorphism.
METHODS We investigated whether polymorphisms in theIL1B and IL1RNgenes were associated with rate of decline of lung function. Genotypes were determined in 284 smokers with a rapid decline in lung function and 306 smokers with no decline in lung function.
RESULTS None of the genotypes was associated with the rate of decline of lung function. However, the distribution of IL1B/IL1RNhaplotypes was different 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.