TY - JOUR
T1 - Variant in promoter region of Platelet-Derived Growth Factor Receptor-α (PDGFRα) gene is associated with the severity and allergic status of childhood asthma
AU - Wu, Lawrence Shih Hsin
AU - Tan, Choon Yee
AU - Wang, Ling Mei
AU - Lin, Cherry Guan Ju
AU - Wang, Jiu Yao
PY - 2006/8
Y1 - 2006/8
N2 - Background: Upregulation of the platelet-derived growth factor receptor-α (PDGFRα) in airway myofibroblast cells is one of the mechanisms of airway remodeling. The genetic association between PDGFRα promoter polymorphism and severity of childhood asthma was examined. Methods: Five single nucleotide polymorphisms (SNPs) at the promoter regions of the PDGFRα 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 PDGFRα, 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 PDGFRα may be one of the susceptible factors for nonallergic asthmatic children. There was also an autocrine effect of lower PDGF-AA and higher PDGFRα expression that might lead to airway remodeling causing the severity of asthma.
AB - Background: Upregulation of the platelet-derived growth factor receptor-α (PDGFRα) in airway myofibroblast cells is one of the mechanisms of airway remodeling. The genetic association between PDGFRα promoter polymorphism and severity of childhood asthma was examined. Methods: Five single nucleotide polymorphisms (SNPs) at the promoter regions of the PDGFRα 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 PDGFRα, 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 PDGFRα may be one of the susceptible factors for nonallergic asthmatic children. There was also an autocrine effect of lower PDGF-AA and higher PDGFRα expression that might lead to airway remodeling causing the severity of asthma.
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U2 - 10.1159/000094180
DO - 10.1159/000094180
M3 - Article
C2 - 16804324
AN - SCOPUS:33747260189
VL - 141
SP - 37
EP - 46
JO - International Archives of Allergy and Immunology
JF - International Archives of Allergy and Immunology
SN - 1018-2438
IS - 1
ER -