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VEGFA variants are associated with pre‐school lung function, but not neonatal lung function
Author(s) -
KreinerMøller E.,
Chawes B. L. K.,
Vissing N. H.,
Koppelman G. H.,
Postma D. S.,
Madsen J. S.,
Olsen D. A.,
Baty F.,
Vonk J. M.,
Kerkhof M.,
Sleiman P.,
Hakonarsson H.,
Mortensen L. J.,
Poorisrisak P.,
Bisgaard H.,
Bønnelykke K.
Publication year - 2013
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12188
Subject(s) - medicine , asthma , cohort , single nucleotide polymorphism , bronchial hyperresponsiveness , vascular endothelial growth factor a , vascular endothelial growth factor , lung , immunology , vegf receptors , genotype , respiratory disease , biology , gene , genetics
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 SNP s in the VEGFA gene in 411 children from the COPSAC 2000 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 SNP s from the same linkage block were associated with FEV 1 (rs699947, P = 1.31E‐05), independent of asthma, and there were suggestive associations between FEV 1/ FVC ratio and rs833052 and maximal mid‐expiratory flow and rs6900017. Replication in the PIAMA cohort showed borderline association between FEV 1 and rs699947 and significant meta‐analysis result. SNP s 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.