title: G894T polymorphism of eNOS gene is a predictor of response to combination of inhaled corticosteroids with long-lasting β2-agonists in asthmatic children.
abstract: OBJECTIVE
  Nitric oxide synthase enzymes have an important role in airway inflammation in asthmatic children. In the present study, the association between eNOS gene polymorphisms and response to inhaled corticosteroids (ICS) and long-lasting β(2)-agonists (LABAs) was investigated.
  
  
  METHODS
  A total of 81 asthmatic children treated with ICS plus LABAs and 96 healthy controls were genotyped for eNOS G894T and -786T/C polymorphisms and their haplotypes using the PCR-RFLP method.
  
  
  RESULTS
  G894T and -786T/C polymorphisms were not associated with asthma susceptibility. Among asthmatic children, 894TT carriers had higher change in forced expiratory volume in 1 s (FEV(1)) in response to ICS plus LABAs compared with 894GG carriers (21.9 ± 3.8 vs 1.6 ± 1.9%; p < 0.001). In responders (FEV(1) change ≥7.5%), frequency of 894TT genotype was significantly higher than in nonresponders (26.2 vs 2.6%, p < 0.001). Results for the -786T/C polymorphism alone were less clear and in most cases nonsignificant.
  
  
  CONCLUSIONS
  The G894T polymorphism was associated with response to ICS and may serve as a useful pharmacogenetic marker of response to ICS plus LABAs in asthmatic children.
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Iordanidou
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Paraskakis
authors.forename: Anna
authors.initials: A
authors.lastname: Tavridou
authors.forename: Peristera
authors.initials: P
authors.lastname: Paschou
authors.forename: Athanasios
authors.initials: A
authors.lastname: Chatzimichael
authors.forename: Vangelis G
authors.initials: VG
authors.lastname: Manolopoulos
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III