The genetic basis of responses to drugs--a rheumatological perspective

The wide individual variations seen in all metabolic pathways which have been examined largely explain differences in drug dose response and toxicity. In some cases, distinct sub-sets occur where the enzyme activity is markedly different from that in the rest of the population (genetic polymorphism). Studies on isolated enzymes and use of restriction fragment length polymorphisms have in some cases helped to elucidate the relevant molecular biology. However, the lack of certain concordance between genotype and phenotype has shown that many questions remain unanswered. As more information becomes available at the molecular level, it may be easier to gain an understanding of the endogenous biochemistry which underlies the human condition. Either genotyping or phenotyping may then be used to predict potential drug side-effects or clinical outcomes.