Unraveling the Genetic Basis of Aspirin Hypersensitivity in Asthma Beyond Arachidonate Pathways

Abstract

Although aspirin-exacerbated respiratory disease (AERD) has attracted a great deal of attention because of its association with severe asthma, it remains widely under-diagnosed in the asthmatic population. Oral aspirin challenge is the best method of diagnosing AERD, but this is a time-consuming procedure with serious complications in some cases. Thus, development of non-invasive methods for easy diagnosis is necessary to prevent unexpected complications of aspirin use in susceptible patients. For the past decade, many studies have attempted to elucidate the genetic variants responsible for risk of AERD. Several approaches have been applied in these genetic studies. To date, a limited number of biologically plausible candidate genes in the arachidonate and immune and inflammatory pathways have been studied. Recently, a genome-wide association study was performed. In this review, the results of these studies are summarized, and their limitations discussed. In addition to the genetic variants, changes in methylation patterns on CpG sites have recently been identified in a target tissue of aspirin hypersensitivity. Finally, perspectives on application of new genomic technologies are introduced; these will aid our understanding of the genetic pathogenesis of aspirin hypersensitivity in asthma.

Upper airways in aspirin-exacerbated respiratory disease

“…Although many genetic variations have been reported to serve as potential markers of the AERD or CRSwNP phenotype, it has been suggested that that HLA DPB1 Ã 0301 reliable genetic marker of CRSwNP in AERD patients, as patients carrying this allele exhibited a significantly higher prevalence of CRSwNP than did those without the allele [31,32]. A recent study [33 & ] showed that serum periostin level is a potential biomarker of AERD, especially AERD with CRSwNP.…”

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

“…954 However, much of the described pathophysiology of AERD is likely explained by genetic variations, of which a number of polymorphisms have been identified that potentially play a causative role. [955][956][957] These polymorphisms are thought to alter enzyme kinetics and receptor sensitivity. As a result the activity of LT-synthase is increased, leading to an overproduction of cysteinyl LTs (cysLTs).…”

Aspirin or Other Nonsteroidal Inflammatory Agent Exacerbated Asthma

“…There are relatively small studies in multiple ethnicities, and many of the reports may reflect specific genetic influences limited to a single population (see Tables E1-E5 in this article's Online Repository at www.jaci-inpractice.org). 17…”