Caution with levodopa dose1. Levodopa challenge test in high dose to confirm PD diagnosis2. Aim for higher dosing of levodopa to produce beneficial effect in carriers of high activity COMTConsider ethnic variations (COMT activity varies in different racial groups)Consider preferential use of COMT inhibitorsConsider lower doses of levodopa and longer inter‐dose intervals. The gene discussed is COMT; the disease is Parkinson disease.