Florez Jose C
Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Simches Research Building-CPZN 5.250, 185 Cambridge Street, Boston, MA, 02114, USA.
Diabetologia. 2017 May;60(5):800-807. doi: 10.1007/s00125-017-4227-1. Epub 2017 Mar 10.
In recent years, technological and analytical advances have led to an explosion in the discovery of genetic loci associated with type 2 diabetes. However, their ability to improve prediction of disease outcomes beyond standard clinical risk factors has been limited. On the other hand, genetic effects on drug response may be stronger than those commonly seen for disease incidence. Pharmacogenetic findings may aid in identifying new drug targets, elucidate pathophysiology, unravel disease heterogeneity, help prioritise specific genes in regions of genetic association, and contribute to personalised or precision treatment. In diabetes, precedent for the successful application of pharmacogenetic concepts exists in its monogenic subtypes, such as MODY or neonatal diabetes. Whether similar insights will emerge for the much more common entity of type 2 diabetes remains to be seen. As genetic approaches advance, the progressive deployment of candidate gene, large-scale genotyping and genome-wide association studies has begun to produce suggestive results that may transform clinical practice. However, many barriers to the translation of diabetes pharmacogenetic discoveries to the clinic still remain. This perspective offers a contemporary overview of the field with a focus on sulfonylureas and metformin, identifies the major uses of pharmacogenetics, and highlights potential limitations and future directions.
近年来，技术和分析方法的进步使得与2型糖尿病相关的基因位点发现数量激增。然而，相较于标准临床风险因素，这些基因位点在改善疾病预后预测方面的能力仍然有限。另一方面，基因对药物反应的影响可能比常见的疾病发病率影响更强。药物遗传学研究结果可能有助于识别新的药物靶点、阐明病理生理学、揭示疾病异质性、帮助在基因关联区域对特定基因进行优先级排序，并推动个性化或精准治疗。在糖尿病领域，药物遗传学概念在单基因亚型（如青少年发病的成年型糖尿病或新生儿糖尿病）中已有成功应用的先例。对于更为常见的2型糖尿病而言，是否会出现类似的见解仍有待观察。随着基因研究方法的进步，候选基因、大规模基因分型和全基因组关联研究的逐步开展已开始产生一些可能改变临床实践的提示性结果。然而，将糖尿病药物遗传学发现转化为临床应用仍存在诸多障碍。本观点文章对该领域进行了当代综述，重点关注磺脲类药物和二甲双胍，确定了药物遗传学的主要用途，并强调了潜在的局限性和未来方向。
