Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece.
Pharmacogenomics. 2011 Aug;12(8):1161-91. doi: 10.2217/pgs.11.65.
Type 2 diabetes mellitus (T2DM) is an increasingly prevalent disease. Several classes of drugs are currently available to treat T2DM patients; however, clinical response to these drugs often exhibits significant variation among individuals. For the oral antidiabetic drug classes of sulfonylureas, nonsulfonylurea insulin secretagogs, biguanides and thiazolidinediones, pharmacogenomic evidence has accumulated demonstrating an association between specific gene polymorphisms and interindividual variability in their therapeutic and adverse reaction effects. These polymorphisms are in genes of molecules involved in metabolism, transport and therapeutic mechanisms of the aforementioned drugs. Overall, it appears that pharmacogenomics has the potential to improve the management of T2DM and help clinicians in the effective prescribing of oral antidiabetic medications. Although pharmacogenomics can explain some of the heterogeneity in dose requirements, response and incidence of adverse effects of drugs between individuals, it is now clearly understood that much of the diversity in drug effects cannot be solely explained by studying the genomic diversity. Epigenomics, the field that focuses on nongenomic modifications that influence gene expression, may expand the scope of pharmacogenomics towards optimization of drug therapy. Therefore, pharmacoepigenomics, the combined analysis of genetic variations and epigenetic modifications, holds promise for the realization of personalized medicine. Although pharmacoepigenomics has so far been evaluated mainly in cancer pharmacotherapy, studies on epigenomic modifications during T2DM development provide useful data on the potential of pharmacoepigenomics to elucidate the mechanisms underlying interindividual response to oral antidiabetic treatment. In summary, the present article focuses on available data from pharmacogenomic studies of oral antidiabetic drugs and also provides an overview of T2DM epigenomic research, which has the potential to boost the development of pharmacoepigenomics in antidiabetic treatment.
2 型糖尿病（T2DM）是一种日益流行的疾病。目前有几类药物可用于治疗 T2DM 患者；然而，这些药物的临床反应在个体之间表现出显著的差异。对于磺酰脲类、非磺酰脲类胰岛素分泌剂、双胍类和噻唑烷二酮类口服抗糖尿病药物类别，已经积累了遗传药理学证据，表明特定基因多态性与这些药物的治疗和不良反应效应的个体间变异性之间存在关联。这些多态性存在于参与上述药物代谢、转运和治疗机制的分子的基因中。总体而言，遗传药理学有可能改善 T2DM 的管理，并帮助临床医生有效地开处口服抗糖尿病药物。虽然遗传药理学可以解释个体间药物剂量需求、反应和不良反应发生率的一些异质性，但现在清楚的是，药物效应的多样性不能仅通过研究基因组多样性来解释。表观遗传学是关注影响基因表达的非基因组修饰的领域，它可能会扩大遗传药理学的范围，以优化药物治疗。因此，药物基因组学，即遗传变异和表观遗传修饰的综合分析，有望实现个性化医疗。虽然药物基因组学迄今为止主要在癌症化疗中进行了评估，但在 T2DM 发展过程中对表观遗传修饰的研究提供了有用的数据，表明药物基因组学在阐明个体对口服抗糖尿病治疗反应的机制方面具有潜力。总之，本文重点介绍了口服抗糖尿病药物遗传药理学研究的现有数据，并概述了 T2DM 表观遗传学研究，这有可能推动抗糖尿病治疗中药物基因组学的发展。
