Complementary Participation of Genetics and Epigenetics in Development of NSAID-exacerbated Respiratory Disease
10.4168/aair.2019.11.6.779
- Author:
Jong Uk LEE
1
;
Jong Sook PARK
;
Hun Soo CHANG
;
Choon Sik PARK
Author Information
1. Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Korea. hschang@sch.ac.kr
- Publication Type:Review
- Keywords:
NSAID hypersensitivity;
asthma;
genetics;
epigenetics
- MeSH:
Anti-Inflammatory Agents, Non-Steroidal;
Asthma;
Computer Simulation;
Cyclooxygenase 1;
Diagnosis;
Dinoprostone;
Epigenomics;
Genetics;
Leukotrienes;
Lipoxins;
Methylation;
Polymorphism, Single Nucleotide;
Prostaglandins
- From:Allergy, Asthma & Immunology Research
2019;11(6):779-794
- CountryRepublic of Korea
- Language:English
-
Abstract:
Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) has attracted a great deal of attention because of its association with severe asthma. However, it remains widely underdiagnosed in asthmatics as well as the general population. Upon pharmacological inhibition of cyclooxygenase 1 by NSAIDs, production of anti-inflammatory prostaglandin E2 and lipoxins ceases, while release of proinflammatory cysteinyl leukotrienes increases. To determine the underlying mechanisms, many studies have attempted to elucidate the genetic variants, such as single nucleotide polymorphisms, responsible for alterations of prostaglandins and leukotrienes, but the results of these genetic studies could not explain the whole genetic pathogenesis of NERD. Accordingly, the field of epigenetics has been introduced as an additional contributor to genomic alteration underlying the development of NERD. Recently, changes in CpG methylation, as one of the epigenetic components, have been identified in target tissues of NERD. This review discusses in silico analyses of both genetic and epigenetic components to gain a better understanding of their complementary roles in the development of NERD. Although the molecular mechanisms underlying NERD pathogenesis remain poorly understood, genetic and epigenetic variations play significant roles. Our results enhance the understanding of the genetic and epigenetic mechanisms involved in the development of NERD and suggest new approaches toward better diagnosis and management.
