title: Variant in promoter region of platelet-derived growth factor receptor-alpha (PDGFRalpha) gene is associated with the severity and allergic status of childhood asthma.
abstract: BACKGROUND
  Upregulation of the platelet-derived growth factor receptor-alpha (PDGFRalpha) in airway myofibroblast cells is one of the mechanisms of airway remodeling. The genetic association between PDGFRalpha promoter polymorphism and severity of childhood asthma was examined.
  
  
  METHODS
  Five single nucleotide polymorphisms (SNPs) at the promoter regions of the PDGFRalpha gene were genotyped in 277 unrelated allergic and nonallergic asthmatic children and 93 age-matched controls. Promoter haplotypes were constructed using SNP genotyping data. The serum level of PDGF-AA, the ligand for PDGFRalpha, was assayed by ELISA kits.
  
  
  RESULTS
  The genotype distribution of SNP rs1800810 (-1171G/C) in nonallergic asthma was significantly different from controls (p=0.038), as well as its allele distribution (p=0.028). Using haplotype analysis, the combination frequency of the low expression of H1 homozygous and heterozygous genotype (H1/H1+H1/H2) was significantly higher in nonallergic asthma as compared to controls (OR=1.94, CI=1.11-3.39, p<0.02). The frequency of H2/H2 homozygous was higher in persistent asthma than in intermittent asthma (p=0.008, OR=2.625). In addition, the PDGF-AA serum level in H2/H2 homozygous haplotype was significantly lower as compared to non-H2/H2 homozygous haplotype both in asthmatic (138.1+/-62.9 vs. 249.7+/-97.1 ng/ml, p<0.05) and nonallergic asthmatic children (113.8+/-38.0 vs. 256.6+/-58.3 ng/ml, p<0.05).
  
  
  CONCLUSIONS
  The developmental deficiency due to the low expression of PDGFRalpha may be one of the susceptible factors for nonallergic asthmatic children. There was also an autocrine effect of lower PDGF-AA and higher PDGFRalpha expression that might lead to airway remodeling causing the severity of asthma.
authors.affiliation: Research Development Division, Vita Genomics Inc., Wugu, Taipei County, Taiwan.
authors.forename: Lawrence Shih-Hsin
authors.initials: LS
authors.lastname: Wu
authors.forename: Choon-Yee
authors.initials: CY
authors.lastname: Tan
authors.forename: Ling-Mei
authors.initials: LM
authors.lastname: Wang
authors.forename: Cherry Guan-Ju
authors.initials: CG
authors.lastname: Lin
authors.forename: Jiu-Yao
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D017479:Receptors, Platelet-Derived Growth Factor