Genetic Basis of Delayed Hypersensitivity Reactions to Drugs in Jewish and Arab Populations

Abstract

Genetic variation can affect drug pharmacokinetics and pharmacodynamics and contribute to variability between individuals in response to medications. Specifically, differences in allele frequencies among individuals and ethnic groups have been associated with variation in their propensity to develop drug hypersensitivity reactions (HSRs). This article reviews the current knowledge on the genetic background of HSRs and its relevance to Jewish and Arab populations. The focus is on human leukocyte antigen (HLA) alleles and haplotypes as predictive markers of HSRs (“immunopharmacogenetics”), but other genes and alleles are described as well. Also discussed is the translation of the pharmacogenetic information to practice recommendations.

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Fig. 1

Abbreviations

ALT:

Alanine aminotransferase

CYP:

Cytochrome P450

DILI:

Drug-induced liver injury

DRESS:

Drug reaction with eosinophilia and systemic symptoms

EMA:

European Medicines Agency

FDA:

Food and Drug Administration

G6PD:

Glucose 6-phosphate dehydrogenase

GME:

Greater Middle East

HLA:

Human leukocyte antigen

HSR:

Hypersensitivity reaction

MHC:

Major histocompatibility complex

NMDP:

National Marrow Donor Program

SCAR:

Severe cutaneous adverse drug reactions

SJS:

Stevens-Johnson syndrome

TEN:

Toxic epidermal necrolysis

TPMT:

Thiopurine S-methyltransferase

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Acknowledgments and Disclosures

This work was supported by funding from the Hebrew University’s School of Pharmacy. Sara Eyal is affiliated with the David R. Bloom Centre for Pharmacy and Dr. Adolf and Klara Brettler Center at The Hebrew University of Jerusalem, Israel.

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Aboukaoud, M., Israel, S., Brautbar, C. et al. Genetic Basis of Delayed Hypersensitivity Reactions to Drugs in Jewish and Arab Populations. Pharm Res 35, 211 (2018). https://doi.org/10.1007/s11095-018-2472-8

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KEY WORDS

  • Arab
  • human leukocyte antigens
  • hypersensitivity reactions
  • Jewish