Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma

Hur, Gyu Young; Broide, David H.

VEGF is a potent inducer of endothelial cell growth, angiogenesis and increased vascular permeability. Therefore, it may play a role in angiogenesis, a feature of airway remodeling in asthma. 20 VEGF messenger RNA (mRNA) expression on the airway mucosa is higher in asthmatic patients than in normal controls 21 ;VEGF levels are associated with the degree of vascularity 21 and are inversely associated with airway caliber and level of AHR. 21 VEGF transgenic mice have an asthma-like phenotype with inflammation, vascular remodeling, edema, mucus metaplasia, myocyte hyperplasia and AHR. 20 Studies have investigated the contribution of SNPs in the VEGF gene to asthma outcomes including decline in lung function in asthma. There was a significant association between VEGF-A SNP rs3025028 and lower lung function measured over a 20-year period from birth throughout childhood with the effect persisting into adulthood in the general population from 2 large birth cohorts 22 (1,246 from Tucson Children's Respiratory Study and 995 from Manchester Asthma and Allergy Study). In addition, in the Childhood Asthma Management Program study, longitudinal analysis confirmed an association of the VEGF genetic polymorphism rs4711750 with FEV1/forced vital capacity (FVC) declines over approximately 4.5 years of observation. 23 The VEGF rs4711750 minor T allele was associated with decreased FEV1/FVC (P = 0.01) in an analysis of 968 children and 1,518 of their parents. So far, no published studies have investigated whether VEGF genetic variants are associated with features of airway remodeling.