title: Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy.
abstract: OBJECTIVE
  Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes.
  
  
  METHODS
  The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects. Fourteen single nucleotide polymorphisms (SNPs) in the YAP1 gene were genotyped in 522 asthmatic subjects and 711 healthy controls. The results were evaluated with traditional frequentist methods and with Bayesian network-based Bayesian multilevel analysis of relevance (BN-BMLA).
  
  
  RESULTS
  The mRNA of all the members of the Hippo/YAP1 pathway could be detected in the induced sputum of both controls and cases. A correlation was found between YAP1 mRNA levels and sputum bronchial epithelial cells (r=0.575, P=0.003). The signal for the FRMD6 protein could be detected in all sputum samples while the YAP1 protein could not be detected in the sputum samples, of the healthy controls and severe asthmatics, but it was detectable in mild asthmatics. The rs2846836 SNP of the YAP1 gene was significantly associated with exercise-induced asthma (odds ratio [OR]=2.1 [1.3-3.4]; P=0.004). The distribution of genotypes of rs11225138 and certain haplotypes of the YAP1 gene showed significant differences between different asthma severity statuses. With BN-BMLA, 2 SNPs, genetic variations in the FRMD6 gene proved to be the most relevant to exercise-induced asthma and allergic rhinitis. These 2 SNPs through allergic rhinitis and exercise-induced asthma were in epistatic interaction with each other.
  
  
  CONCLUSIONS
  Our results provided additional evidence that the FRMD6/Hippo/YAP1 pathway plays a role in the pathogenesis of asthma. If additional studies can confirm these findings, this pathway can be a potential novel therapeutic target in asthma and other inflammatory airway diseases.
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Lili E
authors.initials: LE
authors.lastname: Fodor
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Gézsi
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Ldikó
authors.initials: L
authors.lastname: Ungvári
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Agnes F
authors.initials: AF
authors.lastname: Semsei
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Gál
authors.affiliation: Heim, Pal Children Hospital, Budapest, Hungary.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Nagy
authors.affiliation: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gálffy
authors.affiliation: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors.forename: Lilla
authors.initials: L
authors.lastname: Tamási
authors.affiliation: Heim, Pal Children Hospital, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Kiss
authors.affiliation: Department of Measurement and Information Systems, University of Technology and Economics, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Antal
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.|Heim, Pal Children Hospital, Budapest, Hungary. szalaics@gmail.com.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szalai
keywords: Asthma; YAP1; genetics; rhinitis