Allergy, asthma & immunology research, 2019. 11(6), 779-794, DOI: https://doi.org/10.4168/aair.2019.11.6.779

Complementary Participation of Genetics and Epigenetics in Development of NSAID-exacerbated Respiratory Disease

Jong-Uk Lee, Hun Soo Chang;Jong-Sook Park;Choon-Sik Park

Abstract

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) hasattracted 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. Uponpharmacological inhibition of cyclooxygenase 1 by NSAIDs, production of anti-inflammatoryprostaglandin E2 and lipoxins ceases, while release of proinflammatory cysteinyl leukotrienesincreases. To determine the underlying mechanisms, many studies have attempted toelucidate the genetic variants, such as single nucleotide polymorphisms, responsible foralterations of prostaglandins and leukotrienes, but the results of these genetic studies couldnot explain the whole genetic pathogenesis of NERD. Accordingly, the field of epigeneticshas been introduced as an additional contributor to genomic alteration underlying thedevelopment of NERD. Recently, changes in CpG methylation, as one of the epigeneticcomponents, have been identified in target tissues of NERD. This review discusses in silicoanalyses of both genetic and epigenetic components to gain a better understanding of theircomplementary roles in the development of NERD. Although the molecular mechanismsunderlying NERD pathogenesis remain poorly understood, genetic and epigenetic variationsplay significant roles. Our results enhance the understanding of the genetic and epigeneticmechanisms involved in the development of NERD and suggest new approaches towardbetter diagnosis and management.

• DOI: https://doi.org/10.4168/aair.2019.11.6.779
• ISBN or ISSN: 2092-7355

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.