Several human leucocyte antigen alleles are associated with severe drug hypersensitivity reactions, and Asian Australians have a relatively high risk of carrying such alleles
Prescribing decisions are always personalised, and may consider a patient's age, gender, health conditions and concurrent medications. Pharmacogenetics has the potential to provide additional information to inform these decisions. In a recent MJA article, White and colleagues put forward a call for a sustainable evidence‐based pharmacogenomic screening program for Australia, highlighting DPYD genotyping before fluoropyrimidine chemotherapy as an urgent need.1 DPYD, TPMT and UGT1A1 genotyping are performed to avoid severe toxicities associated with drug over‐exposure in the setting of antineoplastic therapy. With the exception of TPMT, these tests are not typically requested in the community setting. The abbreviations of these and other metabolic enzymes used throughout this article are defined in Box 1.
The full article is accessible to AMA members and paid subscribers. Login to read more or purchase a subscription now.
Please note: institutional and Research4Life access to the MJA is now provided through Wiley Online Library.
- 1. White C, Scott R, Paul CL, Ackland SP. Pharmacogenomics in the era of personalised medicine. Med J Aust 2022; 217: 510‐513. https://www.mja.com.au/journal/2022/217/10/pharmacogenomics‐era‐personalised‐medicine
- 2. Tonk ECM, Gurwitz D, Maitland‐van der Zee AH, Janssens ACJW. Assessment of pharmacogenetic tests: presenting measures of clinical validity and potential population impact in association studies. Pharmacogenomics J 2017; 17: 386‐392.
- 3. Manson LEN, Swen JJ, Guchelaar HJ. Diagnostic test criteria for HLA genotyping to prevent drug hypersensitivity reactions: a systematic review of actionable HLA recommendations in CPIC and DPWG guidelines. Front Pharmacol 2020; 11: 567048.
- 4. Kuruvilla R, Scott K, Pirmohamed SM. Pharmacogenomics of drug hypersensitivity: technology and translation. Immunol Allergy Clin 2022; 42: 335‐355.
- 5. Illing PT, Vivian JP, Purcell AW, et al. Human leukocyte antigen‐associated drug hypersensitivity. Curr Opin Immunol 2013; 25: 81‐89.
- 6. Therapeutic Goods Administration. Database of Adverse Event Notifications (DAEN). https://www.tga.gov.au/safety/safety/safety‐monitoring‐daen‐database‐adverse‐event‐notifications/database‐adverse‐event‐notifications‐daen (viewed Apr 2023).
- 7. Services Australia. Pharmaceutical Benefits Schedule item reports. http://medicarestatistics.humanservices.gov.au/statistics/pbs_item.jsp (viewed Sept 2022).
- 8. Walter SR, Day RO, Gallego B, Westbrook JI. The impact of serious adverse drug reactions: a population‐based study of a decade of hospital admissions in New South Wales, Australia. Br J Clin Pharmacol 2017; 83: 416‐426.
- 9. Australian Bureau of Statistics. Census of Population and Housing: Cultural diversity data summary, 2021. https://www.abs.gov.au/statistics/people/people‐and‐communities/cultural‐diversity‐census/2021/Cultural%20diversity%20data%20summary.xlsx (viewed Aug 2022).
- 10. Gonzalez‐Galarza FF, McCabe A, Santos EJMD, et al. Allele frequency net database (AFND) 2020 update: gold‐standard data classification, open access genotype data and new query tools. Nucleic Acids Res 2020; 48: D783‐D788.
- 11. Ko TM, Tsai CY, Chen SY, et al. Use of HLA‐B*58: 01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ 2015; 351: h4848.
- 12. Chen P, Lin JJ, Lu CS, et al. Carbamazepine‐induced toxic effects and HLA‐B*1502 screening in Taiwan. N Engl J Med 2011; 364: 1126‐1133.
- 13. Jutkowitz E, Dubreuil M, Lu N, et al. The cost‐effectiveness of HLA‐B*5801 screening to guide initial urate‐lowering therapy for gout in the United States. Semin Arthritis Rheum 2017; 46: 594‐600.
- 14. Choi H, Mohit B. Cost‐effectiveness of screening for HLA‐B*1502 prior to initiation of carbamazepine in epilepsy patients of Asian ancestry in the United States. Epilepsia 2019; 60: 1472‐1481.
- 15. Saito Y, Stamp LK, Caudle KE, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA‐B) genotype and allopurinol dosing: 2015 update. Clin Pharmacol Ther 2016; 99: 36‐37.
- 16. Phillips EJ, Sukasem C, Whirl‐Carrillo M, et al. Clinical pharmacogenetics implementation consortium guideline for HLA genotype and use of carbamazepine and oxcarbazepine: 2017 update. Clin Pharmacol Ther 2018; 103: 574‐581.
- 17. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res. 2020; 72: 744‐760.
- 18. Karnes JH, Rettie AE, Somogyi AA, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and HLA‐B genotypes and phenytoin dosing: 2020 update. Clin Pharmacol Ther 2021; 109: 302‐309.
- 19. Australian medicines handbook. https://amhonline.amh.net.au/ (viewed Apr 2022).
- 20. Deng Y, Li S, Zhang L, Jin H, Zou X. Association between HLA alleles and lamotrigine‐induced cutaneous adverse drug reactions in Asian populations: A meta‐analysis. Seizure 2018; 60: 163‐171.
- 21. Lifeblood. Transplantation and immunogenetics services. https://www.lifeblood.com.au/health‐professionals/testing/transplantation‐immunogenetics‐services (viewed Jan 2023).
- 22. James F, Goh MSY, Mouhtouris E, et al. Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS‐SCAR). BMJ Open 2022; 12: e055906.
We thank Jane Carland (St Vincent's Hospital Sydney) and Sophie Stocker (the University of Sydney) for providing valuable suggestions and feedback on the manuscript.
Graeme Suthers is Director of Genetics, Sonic Health Australia, a provider of HLA genotyping tests.