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Interaction between early maternal smoking and variants in TNF and GSTP1 in childhood wheezing.

Authors: Panasevich, S  Lindgren, C  Kere, J  Wickman, M  Pershagen, G  Nyberg, F  Melen, E 
Citation: Panasevich S, etal., Clin Exp Allergy. 2010 Mar;40(3):458-67.
Pubmed: (View Article at PubMed) PMID:20210814
DOI: Full-text: DOI:10.1111/j.1365-2222.2010.03452.x

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. CONCLUSION: Our results suggest that the risk of early childhood wheeze associated with early maternal smoking may be modified by TNF and GSTP1 polymorphisms.

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CRRD Object Information
CRRD ID: 5490991
Created: 2011-09-22
Species: All species
Last Modified: 2011-09-22
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.