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Integrative genomic analysis identifies a role for intercellular adhesion molecule 1 in childhood asthma

Authors

  • Ester M. M. Klaassen,

    Corresponding author
    1. Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands
    • Correspondence

      Ester M. M. Klaassen, Department of Pediatric Pulmonology, Maastricht University Medical Centre, P.O. Box 5800 6202 AZ Maastricht, the Netherlands

      Tel.: +31 43 3872944

      Fax: +31 43 3875246

      E-mail: ester.klaassen@mumc.nl

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  • Kim D. G. van de Kant,

    1. Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands
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  • Quirijn Jöbsis,

    1. Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands
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  • John Penders,

    1. Department of Epidemiology, CAPHRI, MUMC+, Maastricht, the Netherlands
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  • Frederik Jan van Schooten,

    1. Department of Toxicology, School for Nutrition, Toxicology, and Metabolism (NUTRIM), MUMC+, Maastricht, the Netherlands
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  • Marieke Quaak,

    1. Department of Toxicology, School for Nutrition, Toxicology, and Metabolism (NUTRIM), MUMC+, Maastricht, the Netherlands
    2. Department of General Practice, CAPHRI, MUMC+, Maastricht, the Netherlands
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  • Gertjan J. M. den Hartog,

    1. Department of Toxicology, School for Nutrition, Toxicology, and Metabolism (NUTRIM), MUMC+, Maastricht, the Netherlands
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  • Gerard H. Koppelman,

    1. Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
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  • Constant P. van Schayck,

    1. Department of General Practice, CAPHRI, MUMC+, Maastricht, the Netherlands
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  • Guillaume van Eys,

    1. Department of Genetics and Cell Biology, Cardiovascular Research Institute (CARIM), MUMC+, Maastricht, the Netherlands
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  • Edward Dompeling

    1. Department of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands
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Abstract

Background

Childhood asthma is characterized by chronic airway inflammation. Integrative genomic analysis of airway inflammation on genetic and protein level may help to unravel mechanisms of childhood asthma. We aimed to employ an integrative genomic approach investigating inflammation markers on DNA, mRNA, and protein level at preschool age in relationship to asthma development.

Methods

In a prospective study, 252 preschool children (202 recurrent wheezers, 50 controls) from the Asthma DEtection and Monitoring (ADEM) study were followed until the age of six. Genetic variants, mRNA expression in peripheral blood mononuclear cells, and protein levels in exhaled breath condensate for intercellular adhesion molecule 1 (ICAM1), interleukin (IL)4, IL8, IL10, IL13, and tumor necrosis factor α were analyzed at preschool age. At six years of age, a classification (healthy, transient wheeze, or asthma) was based on symptoms, lung function, and medication use.

Results

The ICAM1 rs5498 A allele was positively associated with asthma development (p = 0.02) and ICAM1 gene expression (p = 0.01). ICAM1 gene expression was positively associated with exhaled levels of soluble ICAM1 (p = 0.04) which in turn was positively associated with asthma development (p = 0.01). Furthermore, rs1800872 and rs1800896 in IL10 were associated with altered IL10 mRNA expression (p < 0.01). Exhaled levels of IL4, IL10, and IL13 were positively associated with asthma development (p < 0.01).

Conclusions

In this unique prospective study, we demonstrated that ICAM1 is associated with asthma development on DNA, mRNA, and protein level. Thus, ICAM1 is likely to be involved in the development of childhood asthma.

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