An Updated Review of Genetic Associations With Severe Adverse Drug Reactions: Translation and Implementation of Pharmacogenomic Testing in Clinical Practice

Chuang-Wei Wang; Ivan Arni C Preclaro; Wei-Hsiang Lin; Wen-Hung Chung

doi:10.3389/fphar.2022.886377

An Updated Review of Genetic Associations With Severe Adverse Drug Reactions: Translation and Implementation of Pharmacogenomic Testing in Clinical Practice

Front Pharmacol. 2022 Apr 25:13:886377. doi: 10.3389/fphar.2022.886377. eCollection 2022.

Authors

Chuang-Wei Wang^{1

2

3

4}, Ivan Arni C Preclaro¹, Wei-Hsiang Lin⁵, Wen-Hung Chung^{1

2

3

4

6

7

8

9}

Affiliations

¹ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei and Keelung, Taiwan.
² Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan.
³ Chang Gung Immunology Consortium, Chang Gung Memorial Cital and Chang Gung University, Taoyuan, Taiwan.
⁴ Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China.
⁵ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁶ Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
⁷ Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
⁸ Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁹ Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan.

Abstract

Adverse drug reactions (ADR) remain the major problems in healthcare. Most severe ADR are unpredictable, dose-independent and termed as type B idiosyncratic reactions. Recent pharmacogenomic studies have demonstrated the strong associations between severe ADR and genetic markers, including specific HLA alleles (e.g., HLA-B*15:02/HLA-B*57:01/HLA-A*31:01 for carbamazepine-induced severe cutaneous adverse drug reactions [SCAR], HLA-B*58:01 for allopurinol-SCAR, HLA-B*57:01 for abacavir-hypersensitivity, HLA-B*13:01 for dapsone/co-trimoxazole-induced SCAR, and HLA-A*33:01 for terbinafine-induced liver injury), drug metabolism enzymes (such as CYP2C9*3 for phenytoin-induced SCAR and missense variant of TPMT/NUDT15 for thiopurine-induced leukopenia), drug transporters (e.g., SLCO1B1 polymorphism for statin-induced myopathy), and T cell receptors (Sulfanilamide binding into the CDR3/Vα of the TCR 1.3). This mini review article aims to summarize the current knowledge of pharmacogenomics of severe ADR, and the potentially clinical use of these genetic markers for avoidance of ADR.

Keywords: CYP; adverse drug reactions; drug transporter; drug-induced liver injury; human leukocyte antigens; stevens-johnson syndrome; toxic epidermal necrolysis.

Publication types

Review