Ethnicity and Response to Drug Therapy

Abstract

Hypercholesterolemia is a complex disorder presenting in different forms, including the familial form (FH), with varying underlying aetiology, and contributing substantially to coronary artery disease. Particularly, the FH underlies monogenic changes in genes involved in cholesterol synthesis and transport, including the low density lipoprotein receptor, proprotein convertase sublitisin/kexin type 9 and apolipoprotein B. However, hyperlipidemia is largely a complex interaction of changes in multiple genes with environmental factors, such as diet, overweight and obesity that are controllable by adopting healthy eating habits and exercise, which may vary by ethnicity. Diet alone is often not adequate to achieve the desired lipid lowering effect in individuals harbouring very high cholesterol levels, necessitating the use of lipid lowering medication or other forms of therapy. Antilipidemic drugs fall into (a) bile acid sequestrants (b) cholesterol absorption inhibitors, (c) 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, (d) fibric acid derivatives (e) proprotein convertase subtilisin/kexin type 9 inhibitors, (f) miscellaneous agents and (g) drug combinations. Mutations in their various metabolizing enzymes, particularly the cytochrome P450 family, often lead to partially/non-functional, or even rapid metabolizing phenotypes, triggering great variations in the way individuals respond to drug therapy, which in turn depends on ethnicity. This may produce unexpected outcomes such as therapeutic failure, adverse side effects and toxicity in individuals of different ethnic origin. Hence, in-depth information of the impact of ethnicity on these relationships has the huge potential of achieving optimal quality use of drugs as well as improving the efficacy and safety of antilipidemic therapeutic agents.