title: Interaction between early maternal smoking and variants in TNF and GSTP1 in childhood wheezing.
abstract: BACKGROUND
  Children exposed to tobacco smoke early in life have a higher risk of wheeze. Individual susceptibility may depend on genetic factors.
  
  
  OBJECTIVE
  We studied whether variations in single nucleotide polymorphisms (SNPs) in the TNF, glutathione S transferase P1 (GSTP1) and beta2-adrenoreceptor (ADRB2) genes modify the effect of early maternal smoking on the development of childhood asthma, wheeze and allergic sensitization.
  
  
  METHODS
  In the Swedish prospective birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) (n=4089), data collection included questionnaires to measure tobacco smoke exposure and clinical outcomes up to age 4 and medical examinations with blood sampling for specific IgE measurements and genotyping. We defined early maternal smoking as daily smoking by the mother during pregnancy and/or postnatally. We investigated five TNF, six GSTP1 and three ADRB2 SNPs in 982 selected wheezers and non-wheezers.
  
  
  RESULTS
  An interaction with early maternal smoking was found for three TNF SNPs (-857C/T, Intron 1, Intron 3) with respect to early wheeze (up to 2 years of age). For example, the odds ratio (OR) for developing early wheeze related to early maternal smoking was 2.4 [95% confidence interval (CI) 1.6-3.7] in children with a wild-type CC homozygote genotype of the TNF-857 SNP, while no tobacco-related risk was seen in children carrying the rare T allele. A clear dose response was observed in children with the CC genotype, with an OR of 1.3 (95% CI 1.1-1.5) per each additional pack per week smoked by the mother during pregnancy. A suggestive interaction with early maternal smoking was also seen for three GSTP1 SNPs (Intron 5, Intron 6 and Ile105Val) with respect to transient wheeze, but not for ADRB2 and wheeze phenotypes. No effect modifications were observed for allergic sensitization.
  
  
  CONCLUSIONS
  Our results suggest that the risk of early childhood wheeze associated with early maternal smoking may be modified by TNF and GSTP1 polymorphisms.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. sviatlana.panasevich@ki.se
authors.forename: S
authors.initials: S
authors.lastname: Panasevich
authors.forename: C
authors.initials: C
authors.lastname: Lindgren
authors.forename: J
authors.initials: J
authors.lastname: Kere
authors.forename: M
authors.initials: M
authors.lastname: Wickman
authors.forename: G
authors.initials: G
authors.lastname: Pershagen
authors.forename: F
authors.initials: F
authors.lastname: Nyberg
authors.forename: E
authors.initials: E
authors.lastname: Melén
mesh_terms: D000328:Adult; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics*; D011446:Prospective Studies; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D012135:Respiratory Sounds / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects*; D048069:Tumor Necrosis Factors / Q000235:genetics*
chemical_list: D048069:Tumor Necrosis Factors; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi