Pharmacogenomics
What it means
Inherited variation altering drug response. TPMT deficiency → azathioprine/6-MP myelosuppression (test before starting). DPYD deficiency → 5-FU/capecitabine toxicity. CYP2C19 poor metaboliser → clopidogrel under-activation. **HLA-B*57:01 → abacavir hypersensitivity. HLA-B*15:02 → carbamazepine SJS. G6PD** deficiency → haemolysis with oxidant drugs.
Worked example
Check TPMT activity before azathioprine; if deficient, even normal doses cause profound marrow suppression.
In the exam
Before starting a thiopurine immunosuppressant a doctor checks an enzyme's activity, because deficiency would cause life-threatening myelosuppression at standard doses.
What settles it
TPMT→thiopurines; DPYD→fluoropyrimidines; CYP2C19→clopidogrel; HLA-B*57:01→abacavir — match the gene to the drug.
Classically confused with
CYP450 inducers
Source: BNF; StatPearls