title: Integrated effect of EGFR and PAR-1 signaling crosstalk on airway hyperresponsiveness.
abstract: Among previous genetic studies for asthma, inconsistent findings were often             reported. We used a new approach to examine an integrated effect of haplotype             blocks, newly termed 'haplotype cluster' over two different types of receptors             which share common intracellular pathways on airway hyperresponsiveness (AHR).             We recruited 165 young atopic adults without respiratory symptoms and measured             airway responsiveness to methacholine and classified them into two groups, those             with AHR (PC20 <8.0 mg/ml) and without AHR. In addition, we identified haplotype             blocks or cluster tagging single nucleotide polymorphisms (SNPs) through two genes,             epidermal growth factor receptor (EGFR) and protease activated receptor (PAR)-1,             in all subjects, and compared the frequencies of haplotype block or cluster between             subject groups. Significant differences in the frequencies were observed in the             haplotype blocks within the EGFR gene (rs4947972, rs12718945 and rs2072454; rs4947972,             rs12718945 and rs2227983; and rs4947972, rs12718945 and rs2293347) and the PAR-1             gene (rs37243 and rs253072). An integrated effect was also observed in one haplotype             cluster consisting of both regions of the EGFR gene (rs2293347) and the PAR-1             gene (rs253072) (P=0.0426). Our results suggest the possibility that the integrated             effect of functionally-related EGFR and PAR-1 genes (haplotype cluster) is associated             with susceptibility to AHR.
authors.affiliation: Department of Sports Medicine, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan. tkhr6719@med.osaka-cu.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanazawa
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000235:genetics* / Q000378:metabolism; D001985:Bronchial Provocation Tests; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride; D020641:Polymorphism, Single Nucleotide; D020239:Receptor Cross-Talk; D044463:Receptor, PAR-1 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D044463:Receptor, PAR-1; D016210:Methacholine Chloride; D066246:ErbB Receptors