Background: Upregulation of the platelet-derived growth factor receptor-alpha (PDGFR alpha) in airway myofibroblast cells is one of the mechanisms of airway remodeling. The genetic association between PDGFR alpha promoter polymorphism and severity of childhood asthma was examined. Methods: Five single nucleotide polymorphisms (SNPs) at the promoter regions of the PDGFR alpha 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 PDGFR alpha, 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 HI 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 PDGFR alpha may be one of the susceptible factors for nonallergic asthmatic children. There was also an autocrine effect of lower PDGF-AA and higher PDGFR alpha expression that might lead to airway remodeling causing the severity of asthma.
