Seung-Hyun Kim1, Hyunna Choi2, Moon-Gyung Yoon2, Young-Min Ye2, Hae-Sim Park3. 1. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: kimsh@ajou.ac.kr. 2. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea. 3. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea. Electronic address: hspark@ajou.ac.kr.
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.
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.
Authors: Youming Zhang; Thanushiyan Poobalasingam; Laura L Yates; Simone A Walker; Martin S Taylor; Lauren Chessum; Jackie Harrison; Loukia Tsaprouni; Ian M Adcock; Clare M Lloyd; William O Cookson; Miriam F Moffatt; Charlotte H Dean Journal: Dis Model Mech Date: 2018-01-29 Impact factor: 5.758
Authors: Xiaoliang Wang; Yu-Ru Su; Paneen S Petersen; Stephanie Bien; Stephanie L Schmit; David A Drew; Demetrius Albanes; Sonja I Berndt; Hermann Brenner; Peter T Campbell; Graham Casey; Jenny Chang-Claude; Steven J Gallinger; Stephen B Gruber; Robert W Haile; Tabitha A Harrison; Michael Hoffmeister; Eric J Jacobs; Mark A Jenkins; Amit D Joshi; Li Li; Yi Lin; Noralane M Lindor; Loïc Le Marchand; Vicente Martin; Roger Milne; Robert Maclnnis; Victor Moreno; Hongmei Nan; Polly A Newcomb; John D Potter; Gad Rennert; Hedy Rennert; Martha L Slattery; Steve N Thibodeau; Stephanie J Weinstein; Michael O Woods; Andrew T Chan; Emily White; Li Hsu; Ulrike Peters Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-07-10 Impact factor: 4.090