title: Pharmacogenetics in type 2 diabetes: precision medicine or discovery tool?
abstract: 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.
authors.affiliation: Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA. jcflorez@partners.org.|Center for Genomic Medicine, Massachusetts General Hospital, Simches Research Building-CPZN 5.250, 185 Cambridge Street, Boston, MA, 02114, USA. jcflorez@partners.org.|Metabolism Program, Broad Institute, Cambridge, MA, USA. jcflorez@partners.org.|Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. jcflorez@partners.org.|Department of Medicine, Harvard Medical School, Boston, MA, USA. jcflorez@partners.org.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D057285:Precision Medicine / Q000379:methods*
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Genome-wide association studies; Metformin; Pharmacogenetics; Review; Single nucleotide polymorphisms; Sulfonylureas; TCF7L2; Type 2 diabetes