Pharmacogenetics of hypersensitivity drug reactions

Therapie. 2017 Apr;72(2):231-243. doi: 10.1016/j.therap.2016.12.009. Epub 2017 Jan 3.

Abstract

Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity. Most notable examples include human leukocyte antigen (HLA)-B*57:01 allele and abacavir hypersensitivity syndrome or HLA-B*15:02 and HLA-B*58:01 alleles related to severe cutaneous reactions induced by carbamazepine and allopurinol, respectively. This review aims to explore our current understanding in the field of pharmacogenomics of HLA-associated drug hypersensitivities and its translation into clinical practice for predicting adverse drug reactions.

Keywords: Abacavir; Allopurinol; Carbamazepine; HLA; Hypersensitivity drug reactions.

Publication types

  • Review

MeSH terms

  • Allopurinol / adverse effects
  • Anticonvulsants / adverse effects
  • Carbamazepine / adverse effects
  • Dideoxynucleosides / adverse effects
  • Drug Hypersensitivity / genetics*
  • Drug Hypersensitivity / immunology
  • Enzyme Inhibitors / adverse effects
  • Genetic Predisposition to Disease*
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • Humans
  • Pharmacogenetics
  • Reverse Transcriptase Inhibitors / adverse effects

Substances

  • Anticonvulsants
  • Dideoxynucleosides
  • Enzyme Inhibitors
  • HLA Antigens
  • Reverse Transcriptase Inhibitors
  • Carbamazepine
  • Allopurinol
  • abacavir