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

E Kreiner-Møller1, B L K Chawes, N H Vissing

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

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
|October 25, 2013
PubMed
Summary

Vascular endothelial growth factor (VEGF) gene variants influence childhood lung function development. Specific VEGFA gene variations are linked to lung function changes by school age, not at birth, indicating a post-natal role.

Keywords:
asthmachildinfantrespiratory function testsvascular endothelial growth factor A

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Area of Science:

  • Genetics
  • Pulmonology
  • Pediatrics

Background:

  • Vascular endothelial growth factor (VEGF) plays a role in airway remodeling and asthma development.
  • Investigating VEGFA gene variants and plasma levels is crucial for understanding childhood asthma and lung function.
  • Childhood asthma and lung function are complex conditions influenced by genetic and environmental factors.

Purpose of the Study:

  • To examine the association between VEGFA gene variants and plasma levels with lung function, bronchial hyperresponsiveness, and asthma development in children.
  • To determine if VEGFA gene variants impact lung function at different developmental stages (birth vs. school age).
  • To replicate findings in an independent birth cohort to confirm the role of VEGF in lung development.

Main Methods:

  • Analysis of 13 single nucleotide polymorphisms (SNPs) in the VEGFA gene in 411 children from the COPSAC2000 birth cohort.
  • Prospective asthma diagnosis and lung function measurements at birth and 6 years of age; plasma VEGF levels measured at 18 months.
  • Replication of findings in the PIAMA birth cohort, with Bonferroni adjusted significance levels used.

Main Results:

  • Three VEGFA SNPs (rs699947, rs833052, rs6900017) were associated with lung function (FEV1, FEV1/FVC ratio, maximal mid-expiratory flow) at age six, independent of asthma.
  • Replication in the PIAMA cohort showed a borderline association for FEV1 with rs699947, and a significant meta-analysis result.
  • SNPs near rs699947 were nominally associated with plasma VEGF levels, but VEGF levels were not linked to asthma symptoms or lung function.

Conclusions:

  • VEGF gene variants are associated with lung function development in school-aged children, but not at birth.
  • These findings suggest a significant role for VEGF in the post-natal development of lung function.
  • Further research into VEGF's role in lung development may offer new therapeutic targets for childhood respiratory diseases.