Pharmacogenetics: drug-metabolising enzyme variants and HLA-associated hypersensitivity
How germline variants in CYP2D6, CYP2C19, CYP2C9, VKORC1, TPMT, NUDT15, DPYD and UGT1A1 change drug exposure, how HLA alleles predict severe T-cell mediated reactions to abacavir, carbamazepine and allopurinol, and which tests are funded in Australia.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Pharmacogenetics is how inherited variation changes drug response. Two mechanisms dominate the exam:
- Pharmacokinetic: variants in metabolising enzymes or transporters change exposure to the drug or its active metabolite.
- Immune: particular HLA class I alleles present a drug or drug-modified peptide to CD8 T cells and cause severe type IV reactions.
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Sources
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelinesCPIC / PharmGKB, 2026
- CPIC guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update (November 2018 revision: 50% reduction for activity score 1.5 as well as 1)Clinical Pharmacology and Therapeutics (Amstutz et al., 2018;103:210-6), 2018
- New Medicare Benefits Schedule item for dihydropyrimidine dehydrogenase (DPYD) genotyping (item 73322)AU/NZAustralian Government Department of Health, Disability and Ageing, 2025
- MSAC application 1760: DPYD genotyping to predict fluoropyrimidine-induced toxicityAU/NZMedical Services Advisory Committee, 2024
- HLA-B*5701 screening for hypersensitivity to abacavir (PREDICT-1)New England Journal of Medicine (Mallal et al., 2008;358:568-79), 2008
- Medical genetics: a marker for Stevens-Johnson syndromeNature (Chung et al., 2004;428:486), 2004
- FitzGerald JD et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res 2020;72:744-60American College of Rheumatology, 2020
- HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillinNature Genetics (Daly et al., 2009;41:816-9), 2009
- PharmGKBStanford University, 2026
- Goodman & Gilman's The Pharmacological Basis of Therapeutics (14th ed.)McGraw Hill (Brunton and Knollmann, 2023), 2023
- Last updated
- 14 November 2026
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