title: Can certain genotypes predispose to poor asthma control in children? A pharmacogenetic study of 9 candidate genes in children with difficult asthma.
abstract: OBJECTIVE
  We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control.
  
  
  METHODS
  A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma.
  
  
  RESULTS
  The results indicated that LTA4H A-9188>G, TNFα G-308>A and IL-4Rα A1727>G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p<0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Rα A1199>C, IL-4Rα T1570>C and IL-4Rα A1727>G and CA haplotype of TNFα C-863>A and TNFα G-308>A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively).
  
  
  CONCLUSIONS
  The study revealed multiple SNPs and haplotypes in LTA4H, TNFα and IL4-Rα genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A-9188>G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit.
authors.affiliation: Clinical and Practice Research Group, School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Basima
authors.initials: B
authors.lastname: Almomani
authors.forename: Ahmed F
authors.initials: AF
authors.lastname: Hawwa
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Millership
authors.forename: Liam
authors.initials: L
authors.lastname: Heaney
authors.forename: Isabella
authors.initials: I
authors.lastname: Douglas
authors.forename: James C
authors.initials: JC
authors.lastname: McElnay
authors.forename: Michael D
authors.initials: MD
authors.lastname: Shields
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004843:Epistasis, Genetic; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D006239:Haplotypes; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D019948:Receptors, Interleukin-4; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase