title: Asthma treatment outcome in children is associated with vascular endothelial growth factor A (VEGFA) polymorphisms.
abstract: BACKGROUND
  Asthma is a common chronic disease characterized by airway inflammation and structural remodeling. Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, is elevated in asthma patients. VEGF contributes to airway responsiveness and remodeling. It has been shown that treatment of asthma patients decreases VEGF levels, and inhibition of VEGF diminishes asthma symptoms in mice. Therefore, polymorphisms in the vascular endothelial growth factor A (VEGFA) gene might be associated with asthma treatment response.
  
  
  METHODS
  This study enrolled 131 children with asthma treated with different therapies - specifically, the inhaled corticosteroid (ICS) fluticasone propionate or the leukotriene receptor antagonist (LTRA) montelukast. We performed an association analysis between improvement of lung function - assessed by measurement of the percentage of the predicted forced expiratory volume in 1 second (%predicted FEV(1)), the ratio between the FEV(1) and the forced vital capacity (FEV(1)/FVC) after 6 and 12 months of treatment, and asthma control after 12 months of treatment - and two polymorphisms, rs2146323 and rs833058, in the VEGFA gene.
  
  
  RESULTS
  Polymorphism rs2146323 A>C in VEGFA was associated with response to ICS therapy. Asthma patients with the AA genotype had a greater improvement in the %predicted FEV(1) than those with the AC or CC genotype (p = 0.018). Conversely, the AA genotype in rs2146323 was associated with uncontrolled asthma in patients regularly receiving LTRA therapy (p = 0.020) and a worse FEV(1)/FVC ratio in patients who episodically used LTRA therapy (p = 0.044). Furthermore, polymorphism rs833058 C>T was associated with treatment response to episodically used LTRA therapy. A subgroup of patients with the TT genotype had an improvement in the %predicted FEV(1), compared with no improvement in patients with the CT or CC genotype (p = 0.029).
  
  
  CONCLUSIONS
  Our results showed that treatment response to commonly used asthma therapies (ICS or LTRA) is associated with polymorphisms rs2146323 and rs833058 in VEGFA. With additional replication of this preliminary study, our findings could contribute to the development of individualized asthma therapy.
authors.affiliation: University Clinic of Pulmonary and Allergic Diseases, Golnik, Slovenia. matija.rijavec@klinika-golnik.si
authors.forename: Mateja
authors.initials: M
authors.lastname: Balantic
authors.forename: Matija
authors.initials: M
authors.lastname: Rijavec
authors.forename: Maja
authors.initials: M
authors.lastname: Skerbinjek Kavalar
authors.forename: Stanislav
authors.initials: S
authors.lastname: Suskovic
authors.forename: Mira
authors.initials: M
authors.lastname: Silar
authors.forename: Mitja
authors.initials: M
authors.lastname: Kosnik
authors.forename: Peter
authors.initials: P
authors.lastname: Korosec
mesh_terms: D000085:Acetates / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D003521:Cyclopropanes; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011804:Quinolines / Q000627:therapeutic use; D013440:Sulfides; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D000085:Acetates; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D042461:Vascular Endothelial Growth Factor A; D000068298:Fluticasone; C093875:montelukast