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Clinical & Experimental Allergy

VEGFA variants are associated with pre-school lung function, but not neonatal lung function

Authors

  • E. Kreiner-Møller,

    Corresponding author
    1. COPSAC: Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark
    2. The Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark
    • Correspondence:

      Eskil Kreiner-Møller, Copenhagen Prospective Studies on Asthma in Childhood, Danish Pediatric Asthma Center, Health Sciences, Copenhagen University Hospital, University of Copenhagen, Gentofte, Ledreborg Allé 34, 2820 Gentofte, Denmark.

      E-mail: eskil.kreiner@dbac.dk

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  • B. L. K. Chawes,

    1. COPSAC: Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark
    2. The Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark
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  • N. H. Vissing,

    1. COPSAC: Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark
    2. The Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark
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  • G. H. Koppelman,

    1. Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, Griac research institute, University of Groningen, Groningen, the Netherlands
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  • D. S. Postma,

    1. Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, Groningen, The Netherlands
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  • J. S. Madsen,

    1. Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark
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  • D. A. Olsen,

    1. Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark
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  • F. Baty,

    1. COPSAC: Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark
    2. The Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark
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  • J. M. Vonk,

    1. Department of Epidemiology, University Medical Center Groningen, Griac Research Institute, University of Groningen, Groningen, The Netherlands
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  • M. Kerkhof,

    1. Department of Epidemiology, University Medical Center Groningen, Griac Research Institute, University of Groningen, Groningen, The Netherlands
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  • P. Sleiman,

    1. Center for Applied Genomics and Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • H. Hakonarsson,

    1. Center for Applied Genomics and Division of Human Genetics, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • L. J. Mortensen,

    1. COPSAC: Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark
    2. The Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark
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  • P. Poorisrisak,

    1. COPSAC: Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark
    2. The Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark
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  • H. Bisgaard,

    1. COPSAC: Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark
    2. The Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark
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  • K. Bønnelykke

    1. COPSAC: Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark
    2. The Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark
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Summary

Background

Vascular endothelial growth factor (VEGF) is implicated in airway remodelling and asthma development. We studied VEGFA gene variants and plasma levels and the development of lung function, bronchial hyperresponsiveness and asthma in childhood.

Methods

We analysed 13 SNPs in the VEGFA gene in 411 children from the COPSAC2000 high-risk birth cohort. Asthma was diagnosed prospectively, and lung function measurements were obtained at birth and 6 years of age. Plasma VEGF levels were measured at 18 months of age. We used a Bonferroni adjusted significance level. Findings were replicated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort at age 8.

Results

At age six, three SNPs from the same linkage block were associated with FEV1 (rs699947, P = 1.31E-05), independent of asthma, and there were suggestive associations between FEV1/FVC ratio and rs833052 and maximal mid-expiratory flow and rs6900017. Replication in the PIAMA cohort showed borderline association between FEV1 and rs699947 and significant meta-analysis result. SNPs upstream and nearby rs699947 were nominally associated with VEGF plasma levels. VEGF levels were not associated with asthmatic symptoms or lung function measures.

Conclusions and Clinical Relevance

VEGF gene variants are associated with lung function at school age, but not at birth, suggesting a role of VEGF in post-natal lung function development.

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