Edited by: Stephan Weidinger
Interaction of a 17q12 variant with both fetal and infant smoke exposure in the development of childhood asthma-like symptoms
Article first published online: 3 APR 2012
© 2012 John Wiley & Sons A/S
Volume 67, Issue 6, pages 767–774, June 2012
How to Cite
van der Valk RJP, Duijts L, Kerkhof M, Willemsen SP, Hofman A, Moll HA, Smit H, Brunekreef B, Postma DS, Jaddoe VWV, Koppelman GH, de Jongste J. Interaction of a 17q12 variant with both fetal and infant smoke exposure in the development of childhood asthma-like symptoms. Allergy 2012; 67: 767–774.
- Issue published online: 10 MAY 2012
- Article first published online: 3 APR 2012
- Manuscript Accepted: 27 FEB 2012
- the Netherlands Asthma Fund. Grant Number: AF 3.2.09.081JU
- European Respiratory Society/Marie Curie Joint Research Fellowship. Grant Number: MC 1226-2009
- Developing a Child Cohort Research Strategy for Europe. Grant Number: HEALTH-F2-2009-241504
- the Netherlands Organization for Health Research and Development. Grant Numbers: 90700303, 916.10159
- allergic lung disease;
- asthma epidemiology;
- asthma genetics;
- environmental tobacco smoke;
- pediatric asthma
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).
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.
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.
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.
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.