title: IL13 gene polymorphisms modify the effect of exposure to tobacco smoke on persistent wheeze and asthma in childhood, a longitudinal study.
abstract: BACKGROUND
  Tobacco smoke and genetic susceptibility are risk factors for asthma and wheezing. The aim of this study was to investigate whether there is a combined effect of interleukin-13 gene (IL13) polymorphisms and tobacco smoke on persistent childhood wheezing and asthma.
  
  
  METHODS
  In the Isle of Wight birth cohort (UK, 1989-1999), five IL13 single nucleotide polymorphisms (SNPs): rs1800925 (-1112C/T), rs2066960, rs1295686, rs20541 (R130Q) and rs1295685 were genotyped. Parents were asked whether their children had wheezed in the last 12 months at ages 1, 2, 4 and 10 years. Children who reported wheeze in the first 4 years of life and also had wheezing at age 10 were classified as early-onset persistent wheeze phenotype; non-wheezers never wheezed up to age 10. Persistent asthma was defined as having a diagnosis of asthma both during the first four years of life and at age 10. Logistic regression methods were used to analyze data on 791 children with complete information. Potential confounders were gender, birth weight, duration of breast feeding, and household cat or dog present during pregnancy.
  
  
  RESULTS
  Maternal smoking during pregnancy was associated with early-onset persistent wheeze (OR 2.93, p < 0.0001); polymorphisms in IL13 were not (OR 1.15, p = 0.60 for the common haplotype pair). However, the effect of maternal smoking during pregnancy was stronger in children with the common IL13 haplotype pair compared to those without it (OR 5.58 and OR 1.29, respectively; p for interaction = 0.014). Single SNP analysis revealed a similar statistical significance for rs20541 (p for interaction = 0.02). Comparable results were observed for persistent childhood asthma (p for interaction = 0.03).
  
  
  CONCLUSIONS
  This is the first report that shows a combined effect of in utero exposure to smoking and IL13 on asthma phenotypes in childhood. The results emphasize that genetic studies need to take environmental exposures into account, since they may explain contradictory findings.
authors.affiliation: Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. asadeghn@wfubmc.edu
authors.forename: Alireza
authors.initials: A
authors.lastname: Sadeghnejad
authors.forename: Wilfried
authors.initials: W
authors.lastname: Karmaus
authors.forename: S Hasan
authors.initials: SH
authors.lastname: Arshad
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kurukulaaratchy
authors.forename: Marianne
authors.initials: M
authors.lastname: Huebner
authors.forename: Susan
authors.initials: S
authors.lastname: Ewart
mesh_terms: D001249:Asthma / Q000453:epidemiology* / Q000235:genetics*; D015984:Causality; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006801:Humans; D007223:Infant; D018793:Interleukin-13 / Q000235:genetics*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012135:Respiratory Sounds / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D018793:Interleukin-13