title: Dipeptidyl-peptidase 10 as a genetic biomarker for the aspirin-exacerbated respiratory disease phenotype.
abstract: BACKGROUND
  Aspirin-exacerbated respiratory disease (AERD) is an endotype of severe and eosinophilic adult asthma characterized by chronic rhinosinusitis with nasal polyps and hypersensitivity to aspirin and/or nonsteroidal anti-inflammatory drugs. A genetic contribution of dipeptidyl-peptidase 10 (DPP10) to asthma susceptibility and lung function decline has been reported. However, little is known about the role of DPP10 in the pathogenesis of AERD.
  
  
  OBJECTIVE
  To identify genetic variants of DPP10 that confer susceptibility to AERD or severe asthma.
  
  
  METHODS
  A case-control association study of DPP10 gene polymorphisms was performed in 3 groups of patients: 274 with AERD, 272 with aspirin-tolerant asthma, and 99 normal healthy controls. The rs17048175 single-nucleotide polymorphism was targeted based on a preliminary genomewide association study using an Affymetrix genomewide human single-nucleotide polymorphism array in a Korean population. DPP10, 15-hydroxyeicosatetraenoic acid, and YKL-40/chitinase-3-like protein were measured by enzyme-linked immunosorbent assay in sera taken from the study subjects.
  
  
  RESULTS
  There was a significant association between rs17048175 and the AERD phenotype, but not with aspirin-tolerant asthma. The DPP10 level was significantly higher in sera from patients with AERD compared with patients with aspirin-tolerant asthma and control subjects (P = .021 and P < .001, respectively). In addition, there was a significant difference of serum DPP10 level according to the single-nucleotide polymorphism (P = .001). Serum DPP10 level showed a strong correlation with 15-hydroxyeicosatetraenoic acid (r = 0.226, P = .017) and YKL-40 (r = 0.364, P = .004).
  
  
  CONCLUSIONS
  This study suggests a genetic contribution of rs17048175 to DPP10 in eosinophilic inflammation induction in the airways and to AERD susceptibility.
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: kimsh@ajou.ac.kr.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyunna
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Moon-Gyung
authors.initials: MG
authors.lastname: Yoon
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Ye
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: hspark@ajou.ac.kr.
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D001241:Aspirin / Q000276:immunology*; D055963:Asthma, Aspirin-Induced / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D000071451:Chitinase-3-Like Protein 1; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics*; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D037102:Lectins / Q000097:blood; D008297:Male; D009298:Nasal Polyps / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006893:Hydroxyeicosatetraenoic Acids; D037102:Lectins; C095123:15-hydroxyeicosatrienoic acid; C476879:DPP10 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D001241:Aspirin