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).

CONCLUSION: This study suggests a genetic contribution of rs17048175 to DPP10 in eosinophilic inflammation induction in the airways and to AERD susceptibility.