title: IL13 promoter polymorphism 1112C/T modulates the adverse effect of tobacco smoking on lung function.
abstract: BACKGROUND
  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).
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Center for Human Genomics and Department of Medicine, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA. asadeghn@wfubmc.edu
authors.forename: Alireza
authors.initials: A
authors.lastname: Sadeghnejad
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.forename: David A
authors.initials: DA
authors.lastname: Sterling
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Jill A
authors.initials: JA
authors.lastname: Ohar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics* / Q000502:physiology; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000453:epidemiology / Q000503:physiopathology*; D014797:Vital Capacity / Q000235:genetics* / Q000502:physiology
chemical_list: D018793:Interleukin-13