Interaction of a 17q12 variant with both fetal and infant smoke exposure in the development of childhood asthma-like symptoms

Autor: A. Hofman, Henriette A. Moll, J. C. de Jongste, Vincent W. V. Jaddoe, Dirkje S. Postma, Gerard H. Koppelman, Henriette A. Smit, Bert Brunekreef, R. J. P. van der Valk, Liesbeth Duijts, Sten P. Willemsen, Marjan Kerkhof
Přispěvatelé: Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS, Faculteit Medische Wetenschappen/UMCG, Groningen Research Institute of Pharmacy, Groningen Research Institute for Asthma and COPD (GRIAC), Pediatrics, Gastroenterology & Hepatology, Epidemiology, Erasmus MC other
Rok vydání: 2012
Předmět:
TOBACCO-SMOKE
Adult
Male
Linkage disequilibrium
Pediatrics
medicine.medical_specialty
Immunology
IN-UTERO
environmental tobacco smoke
Single-nucleotide polymorphism
Tobacco smoke
03 medical and health sciences
Fetus
0302 clinical medicine
Humans
Immunology and Allergy
Medicine
Genetic Predisposition to Disease
MATERNAL SMOKING
030212 general & internal medicine
ENVIRONMENT INTERACTIONS
allergic lung disease
Prospective cohort study
asthma genetics
17Q21 VARIANTS
Netherlands
Asthma
Pregnancy
business.industry
PIAMA BIRTH COHORT
asthma epidemiology
ORMDL3
Infant
Newborn
Infant
Odds ratio
medicine.disease
GENE
3. Good health
LIFE
RESPIRATORY SYMPTOMS
030228 respiratory system
International (English)
Female
Tobacco Smoke Pollution
business
pediatric asthma
Chromosomes
Human
Pair 17
Cohort study
Zdroj: Allergy; Vol 67
Allergy, 67(6), 767-774. Wiley-Blackwell
Allergy, 67(6), 767-774. Wiley-Blackwell Publishing Ltd
ISSN: 0105-4538
Popis: Background Gene variants on chromosome 17q12-21 are associated with an increased risk of childhood-onset asthma, a risk known to be modified by environmental tobacco smoke (ETS). Objectives To assess whether the association of rs2305480 on chromosome 17q12 in the GSDML gene with asthma-like symptoms in the first 4 years of life is modified by smoke exposure during fetal and early postnatal life. Methods We used data from two independent prospective cohort studies from fetal life onwards in the Netherlands. We genotyped rs2305480 and assessed maternal smoking during pregnancy and ETS exposure at the age of 2. Asthma-like symptoms, defined as any reported wheezing, shortness of breath or dry nocturnal cough, were reported by parents when the children were 1, 2, 3, and 4 years. Analyses were based on a total group of 4461 Caucasian children. Results The G risk-allele of rs2305480 was associated with asthma-like symptoms [overall odds ratio 1.17 (1.11, 1.24), 2.66E-9]. The effect of rs2305480 on asthma-like symptoms was stronger among children who were exposed to smoke during fetal life (P-interaction = 0.04). Smoke exposure in early postnatal life was also associated with an increased effect of the 17q12 single nucleotide polymorphism (SNP) on asthma-like symptoms (P-interaction = 5.06E-4). These associations were consistent in both cohorts. Conclusion A 17q12 variant, rs2305480, was associated with asthma-like symptoms in preschool children, and this association was modified by smoke exposure already during fetal life, and in infancy. Further investigation regarding SNPs in linkage disequilibrium with rs2305480 in relation to pathophysiological pathways is needed.
Databáze: OpenAIRE
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