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

Alireza Sadeghnejad, Deborah A. Meyers, Matteo Bottai, David Sterling, Eugene R. Bleecker, Jill A. Ohar

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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 FEV1 and FEV1/FVC ratio are modulated by IL13 polymorphisms. Methods: Smokers (≥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 FEV1 and FEV1/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 FEV1 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 %predicted FEV1 (P for interaction < 0.03 for mean %predicted FEV1 and < 0.0001 for 90th percentile %predicted FEV1). Every 20-pack-year increment in smoking was associated with a 2.4% reduction in mean %predicted FEV1 in the common homozygous (CC) or heterozygous (CT) promoter genotypes, and an 8.2% reduction in mean%predicted FEV1 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.

Original languageEnglish
Pages (from-to)748-752
Number of pages5
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume176
Issue number8
DOIs
StatePublished - 15 Oct 2007

Keywords

  • Gene-environment interaction
  • Interleukin 13
  • Polymorphism
  • Tobacco smoke

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