Genetic susceptibility to adverse drug reactions

Adverse drug reactions (ADRs) are a major clinical problem. Genetic factors can determine individual susceptibility to both dose-dependent and dose-independent ADRs. Determinants of susceptibility include kinetic factors, such as gene polymorphisms in cytochrome P450 enzymes, and dynamic factors, such as polymorphisms in drug targets. The relative importance of these factors will depend on the nature of the ADR; however, it is likely that more than one gene will be involved in most instances. In the future, whole genome single nucleotide polymorphism (SNP) profiling might allow an unbiased method of determining genetic predisposing factors for ADRs, but might be limited by the lack of adequate numbers of patient samples. The overall clinical utility of genotyping in preventing ADRs needs to be proven by the use of prospective randomized controlled clinical trials.