IL13 promoter polymorphism 1112C/T modulates the adverse effect of tobacco smoking on lung function

RATIONALE: Although the duration and amount of cigarette smoking correlate 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). OBJECTIVES: We investigated whether the relationships between smoking and the lung function measures FEV(1) and FEV(1)/FVC ratio are modulated by IL13 polymorphisms. METHODS: Smokers (>or=20 pack-years), aged at least 40 years 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 %predicted FEV(1) and FEV(1)/FVC ratio. Age, sex, and current smoking status were included as confounders. MEASUREMENTS AND MAIN RESULTS: The number of pack-years smoked was associated with a lower value for both %predicted FEV(1) and FEV(1)/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 %predicted FEV(1) (P for interaction < 0.03 for mean %predicted FEV(1) and < 0.0001 for 90th percentile %predicted FEV(1)). Every 20-pack-year increment in smoking was associated with a 2.4% reduction in mean %predicted FEV(1) in the common homozygous (CC) or heterozygous (CT) promoter genotypes, and an 8.2% reduction in mean %predicted FEV(1) 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.