Original Article

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

  1. R. J. P. van der Valk1,2,3,
  2. L. Duijts1,2,3,
  3. M. Kerkhof4,
  4. S. P. Willemsen5,
  5. A. Hofman1,3,
  6. H. A. Moll2,
  7. H. A. Smit6,7,
  8. B. Brunekreef6,8,
  9. D. S. Postma9,
  10. V. W. V. Jaddoe1,2,3,
  11. G. H. Koppelman10,
  12. J. C. de Jongste2,*

Article first published online: 3 APR 2012

DOI: 10.1111/j.1398-9995.2012.02819.x

Issue

Allergy

Allergy

Volume 67, Issue 6, pages 767–774, June 2012

Additional Information

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.

Author Information

  1. 1

    The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands

  2. 2

    Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands

  3. 3

    Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

  4. 4

    Department of Epidemiology, University Medical Center Groningen, GRIAC research Institute, University of Groningen, Groningen, the Netherlands

  5. 5

    Department of Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands

  6. 6

    Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands

  7. 7

    Centre for Prevention and Health Services Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands

  8. 8

    Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands

  9. 9

    Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, GRIAC Research Institute, University of Groningen, Groningen, the Netherlands

  10. 10

    Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, GRIAC Research Institute, University of Groningen, Groningen, the Netherlands

*Correspondence
Johan C. de Jongste, Department of Pediatrics, Erasmus University Medical Center0, Sophia Children's Hospital, PO Box 2060, 3000 CB Rotterdam, the Netherlands.
Tel.: +31 10 703 62 63
Fax: +31 10 703 68 11
E-mail: j.c.dejongste@erasmusmc.nl

  1. Edited by: Stephan Weidinger

Publication History

  1. Issue published online: 10 MAY 2012
  2. Article first published online: 3 APR 2012
  3. Manuscript Accepted: 27 FEB 2012

Funded by

  • 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

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (283K)

Keywords:

  • allergic lung disease;
  • asthma epidemiology;
  • asthma genetics;
  • environmental tobacco smoke;
  • pediatric asthma

Abstract

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.

View Full Article (HTML) Get PDF (283K)