Variant in promoter region of Platelet-Derived Growth Factor Receptor-α (PDGFRα) gene is associated with the severity and allergic status of childhood asthma

Lawrence Shih Hsin Wu, Choon Yee Tan, Ling Mei Wang, Cherry Guan Ju Lin, Jiu Yao Wang

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalInternational Archives of Allergy and Immunology
Volume141
Issue number1
DOIs
Publication statusPublished - 2006 Aug

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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