Published ahead of print on July 5, 2007, doi:10.1164/rccm.200704-543OC Am. J. Respir. Crit. Care Med., Volume 176, Number 8, October 2007, 748-752 A more recent version of this article appeared on October 15, 2007
Submitted on April 5, 2007 IL13 Promoter Polymorphism -1112C/T Modulates the Adverse Effect of Tobacco Smoking on Lung FunctionAlireza Sadeghnejad1*,1 Center for Human Genomics and Department of Medicine and Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC, USA, 2 Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA, 3 School of Public Health, Saint Louis University, St. Louis, MO, USA * To whom correspondence should be addressed. E-mail: asadeghn{at}wfubmc.edu.
RATIONALE: Although the duration and amount of cigarette smoking correlates with reduction in pulmonary function, there is still variation among individual responses. IL-13 is involved in pulmonary inflammation, remodeling and susceptibility to chronic obstructive pulmonary disease (COPD). We investigated whether the relationships between smoking and the lung function measures FEV1 and FEV1/FVC ratio are modulated by IL13 polymorphisms.
METHODS: Smokers ( Key words: interleukin 13, polymorphism, tobacco smoke, gene-environment interaction
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20 pack-years), at least 40 year old (n = 1,073) were genotyped for three single nucleotide polymorphisms (SNPs, -1112C/T (rs1800925), +2044G/A (rs20541, R130Q) and +2525G/A (rs1295685)) in the IL13 gene. Linear, quantile, and logistic regression methods were used to assess the effect of cigarette smoking (pack-years), IL13 polymorphisms and their interaction on percent-predicted (pp) FEV1 and FEV1/FVC ratio. Age, sex and current smoking status were included as confounders.
RESULTS: The number of pack-years smoked was associated with a lower value for both ppFEV1 and FEV1/FVC (p < 0.001).The three SNPs were not associated with lung function measures, however there was a significant combined effect between smoking and the promoter polymorphism -1112C/T on ppFEV1 (p for interaction < 0.03 for mean ppFEV1 and < 0.0001 for 90th percentile ppFEV1). Every 20 pack-year increment in smoking was associated with a 2.4% reduction in mean ppFEV1 in the common homozygous (CC) or heterozygous (CT) promoter genotypes, and an 8.2% reduction in mean ppFEV1 in minor allele homozygotes (TT, recessive model).
CONCLUSIONS: An IL13 polymorphism in the promoter region may modulate the adverse effects of cigarette smoking on pulmonary function in long-term cigarette smokers.
