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.
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.
Authors: Salome Scholtens; Dirkje S Postma; Miriam F Moffatt; Sviatlana Panasevich; Raquel Granell; A John Henderson; Erik Melén; Fredrik Nyberg; Göran Pershagen; Deborah Jarvis; Adaikalavan Ramasamy; Matthias Wjst; Cecilie Svanes; Emmanuelle Bouzigon; Florence Demenais; Francine Kauffmann; Valérie Siroux; Erika von Mutius; Markus Johannes Ege; Charlotte Braun-Fahrländer; Jon Genuneit; Bert Brunekreef; Henriette A Smit; Alet H Wijga; Marjan Kerkhof; Ivan Curjuric; Medea Imboden; Gian A Thun; Nicole Probst-Hensch; Maxim B Freidin; Elena Iu Bragina; I A Deev; V P Puzyrev; Denise Daley; Julie Park; Allan Becker; Moira Chan-Yeung; Anita L Kozyrskyj; Peter Pare; Ingo Marenholz; Susanne Lau; Thomas Keil; Young-Ae Lee; Michael Kabesch; Cisca Wijmenga; Lude Franke; Ilja M Nolte; Judith Vonk; Ashish Kumar; Martin Farrall; William O C M Cookson; David P Strachan; Gerard H Koppelman; H Marike Boezen Journal: J Allergy Clin Immunol Date: 2013-12-06 Impact factor: 10.793
Authors: Elaina A MacIntyre; Michael Brauer; Erik Melén; Carl Peter Bauer; Mario Bauer; Dietrich Berdel; Anna Bergström; Bert Brunekreef; Moira Chan-Yeung; Claudia Klümper; Elaine Fuertes; Ulrike Gehring; Anna Gref; Joachim Heinrich; Olf Herbarth; Marjan Kerkhof; Gerard H Koppelman; Anita L Kozyrskyj; Göran Pershagen; Dirkje S Postma; Elisabeth Thiering; Carla M T Tiesler; Christopher Carlsten Journal: Environ Health Perspect Date: 2014-01-24 Impact factor: 9.031