[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Pharmacogenetics [Pharmacology](https://durgical.com/en/pharmacology/) · Topic # Pharmacogenetics How inherited differences in genes change the way a person handles a drug or reacts to it, and when a genetic test can guide treatment. Updated 2026-11-01 Pharmacogenetics studies gene variants that change drug response. Some variants change pharmacokinetics (enzymes that activate or clear a drug), others change the target or the immune system's reaction. Regulators list these gene–drug pairs in labels, and expert groups such as CPIC publish guidance on how to use test results. ## Key points - Metaboliser types: poor, intermediate, normal, rapid and ultrarapid, depending on how many working copies of an enzyme gene a person has. - Warfarin: CYP2C9 and VKORC1 variants explain most of the known variability in dose requirement (warfarin label). - Clopidogrel: people with two loss-of-function CYP2C19 alleles activate less drug; the label's boxed warning suggests another P2Y12 inhibitor for them. - Codeine and tramadol: CYP2D6 ultrarapid metabolisers make more active opioid (risk of toxicity); poor metabolisers get little effect. - Immune reactions: HLA-B*57:01 and abacavir hypersensitivity; HLA-B*15:02 and carbamazepine-induced Stevens–Johnson syndrome/toxic epidermal necrolysis. ## Enzyme variants (pharmacokinetics) - CYP2C9 (and VKORC1, the warfarin target): warfarin sensitivity - CYP2C19: clopidogrel activation - CYP2D6: codeine and tramadol activation; many antidepressants - TPMT and NUDT15: azathioprine and mercaptopurine; low activity causes severe myelosuppression - DPYD: fluorouracil and capecitabine; deficiency causes severe toxicity - BCHE (plasma cholinesterase): suxamethonium; atypical enzyme prolongs paralysis - NAT2 (acetylation): slow acetylators keep sulfapyridine (from sulfasalazine) longer ## Immune and target variants - HLA-B*57:01: abacavir hypersensitivity (screening before starting) - HLA-B*15:02: carbamazepine and severe skin reactions, mainly in people of Asian ancestry - G6PD deficiency: haemolysis with primaquine, dapsone or rasburicase - RYR1 variants: malignant hyperthermia with volatile anaesthetics and suxamethonium ## Using the results The FDA Table of Pharmacogenomic Biomarkers in Drug Labeling lists which labels mention a gene and in which section (boxed warning, dosing, contraindications). CPIC guidelines translate a genotype into a recommendation (use as usual, adjust, or choose another drug). A result is lifelong, so it is worth recording in the patient's chart. ## Limits Genes explain only part of the variation: age, kidney and liver function, interactions, adherence and diet also matter. Allele frequencies differ between populations, including within Latin America, so data from one population may not fit another. ## Memory aid Prodrug + poor metaboliser = too little effect. Active drug + poor metaboliser = too much. Prodrug + ultrarapid = too much, fast. ## Test yourself Think of the answer, then tap the question to see it. ## Why does a CYP2C19 poor metaboliser get less benefit from clopidogrel? Clopidogrel is a prodrug activated mainly by CYP2C19; with two loss-of-function alleles less active metabolite forms, so platelet inhibition is weaker. ## Why can codeine be dangerous in a CYP2D6 ultrarapid metaboliser? CYP2D6 converts codeine to morphine; ultrarapid metabolisers make more morphine faster, with a risk of opioid toxicity. ## Which test is done before starting abacavir and why? HLA-B*57:01, because carriers have a high risk of a serious hypersensitivity reaction. ## What do TPMT and NUDT15 variants change? They reduce the breakdown of thiopurines such as azathioprine and mercaptopurine, raising the risk of severe bone marrow suppression. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/topics/pharmacogenetics/) ## Related classes - [Vitamin K antagonists](https://durgical.com/en/pharmacology/classes/vitamin-k-antagonists/) - [Antiplatelet drugs](https://durgical.com/en/pharmacology/classes/antiplatelet-drugs/) - [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/) - [Antimetabolites](https://durgical.com/en/pharmacology/classes/antimetabolites/) - [Neuromuscular blockers](https://durgical.com/en/pharmacology/classes/neuromuscular-blockers/) ## Example drugs - [Warfarin](https://durgical.com/en/pharmacology/warfarin/) - [Clopidogrel](https://durgical.com/en/pharmacology/clopidogrel/) - [Codeine](https://durgical.com/en/pharmacology/codeine/) - [Tramadol](https://durgical.com/en/pharmacology/tramadol/) - [Abacavir](https://durgical.com/en/pharmacology/abacavir/) - [Carbamazepine](https://durgical.com/en/pharmacology/carbamazepine/) - [Azathioprine](https://durgical.com/en/pharmacology/azathioprine/) - [Fluorouracil](https://durgical.com/en/pharmacology/fluorouracil/) - [Dapsone](https://durgical.com/en/pharmacology/dapsone/) - [Rasburicase](https://durgical.com/en/pharmacology/rasburicase/) - [Suxamethonium](https://durgical.com/en/pharmacology/suxamethonium/) - [Sulfasalazine](https://durgical.com/en/pharmacology/sulfasalazine/) [← All of pharmacology](https://durgical.com/en/pharmacology/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Table of Pharmacogenomic Biomarkers in Drug Labeling](https://www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling) (U.S. Food and Drug Administration, 2026); [What is pharmacogenomics?](https://medlineplus.gov/genetics/understanding/genomicresearch/pharmacogenomics/) (MedlinePlus Genetics (U.S. National Library of Medicine), 2026); [DailyMed - WARFARIN SODIUM tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ad881e0-ca41-42ad-9d7d-eb85b3a30af0) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - CLOPIDOGREL BISULFATE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ab32a331-2cea-453b-bba1-5451d38edd73) (DailyMed (U.S. National Library of Medicine), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/topics/pharmacogenetics/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/topics/pharmacogenetics/