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Pharmacogenomics in Aspirin Intolerance

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Abstract:

Polymorphisms in drug-related enzymes and receptors are often strongly related to altered drug response and to the risk of developing drug intolerance. Aspirin, usually available as an over-the-counter drug, is one of the most used drugs worldwide and is a common cause of drug intolerance events. Aspirin undergoes polymorphic metabolism. Among the enzymes involved in aspirin biodisposition a major role is played by the enzymes UDP-glucuronosyltransferase UGT1A6, cytochrome P450 CYP2C9 and the xenobiotic/ medium chain fatty acid:CoA ligase ACSM2, although other UGTs and ACSMs enzymes may significantly contribute to aspirin metabolism. UGT1A6, CYP2C9 and ACSM2 are polymorphic, as well as PTGS1 and PTGS2, the genes coding for the enzymes cyclooxygenases COX1 and COX2, respectively.

The present review analyzes the importance of genetic variations in enzymes involved in the metabolism and in the effects of aspirin and common polymorphisms related to aspirin intolerance, and it raises hypotheses on genetic factors related to altered response to aspirin that require further investigation. Major polymorphisms related to aspirin biodisposition are rs2070959, rs1105879 and rs6759892 for the UGT1A6 gene, rs1133607 for the ACSM2 gene, and rs1799853, rs1057910, rs28371686, rs9332131 and rs28371685 for the CYP2C9 gene. Regarding aspirin effects, major PGTS1 targets are rs3842787 and rs5789 for European subjects, and rs3842789 and rs3842792 for African subjects. For the PTGS2 gene nonsynonymous SNPs are likely to be of low relevance because of the influence of transcriptional and posttranscriptional factors. Combined studies for the above mentioned polymorphisms and those corresponding to other genes related to aspirin intolerance will provide excellent tools to identify individuals with a high risk to develop intolerance to aspirin.



Keywords: Pharmacogenomics; aspirin; intolerance; polymorphisms

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/138920009790711814

Publication date: November 1, 2009

More about this publication?
  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
ben/cdm/2009/00000010/00000009/art00006
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