Prospects and limits of pharmacogenetics: the thiopurine methyl transferase (TPMT) experience.

摘要: Thiopurine drug metabolism is a quintessential case of pharmacogenetics. A wealth experimental and clinical data on polymorphisms in the thiopurine metabolizing enzyme methyl transferase (TPMT) has been generated past decade. Pharmacogenetic testing prior to treatment already being practiced some extent context, it likely that will be among first pharmacogenetic tests applied regular basis. We analyzed published TPMT identified lessons learned for future implementation pharmacogenetics thiopurines as well other fields. These include need comprehensive unbiased allele frequencies relevant broad range populations worldwide. The nature frequency gene ethnic groups still matter speculation, vast majority studies distribution are limited only small subset alleles populations. Secondly, an appreciation limits warranted, can help avoiding some, but by far not all adverse effects therapy. An analysis six correlating genotype revealed average 78% reactions were associated with polymorphisms. thus eliminate careful monitoring reactions. Finally, approach toward dose increases patients high activity necessary, TPMT-mediated methylation generates possibly hepatotoxic byproduct.