Pharmacogenetics of Oral Antidiabetic Drugs. (13th November 2013)

• Record Type: Journal Article
• Authors: Becker, Matthijs L.; Pearson, Ewan R.; Tkáč, Ivan
• Other Names: Hussain Khalid Academic Editor.
• Is Part Of: International journal of endocrinology. Volume 2013(2013)
• Publication Date: 2013-11-13
• Subjects: Endocrinology -- Periodicals; Endocrinology; Endocrinology -- Periodicals; Endocrine System Diseases -- Periodicals; Periodicals; 616.4
• DOI: 10.1155/2013/686315
• Languages: English
• ISSNs: 1687-8337

Abstract

Abstract : Oral antidiabetic drugs (OADs) are used for more than a half-century in the treatment of type 2 diabetes. Only in the last five years, intensive research has been conducted in the pharmacogenetics of these drugs based mainly on the retrospective register studies, but only a handful of associations detected in these studies were replicated. The gene variants in CYP2C9, ABCC8/KCNJ11, and TCF7L2 were associated with the effect of sulfonylureas. CYP2C9 encodes sulfonylurea metabolizing cytochrome P450 isoenzyme 2C9, ABCC8 and KCNJ11 genes encode proteins constituting ATP-sensitive K + channel which is a therapeutic target for sulfonylureas, and TCF7L2 is a gene with the strongest association with type 2 diabetes. SLC22A1, SLC47A1, and ATM gene variants were repeatedly associated with the response to metformin. SLC22A1 and SLC47A1 encode metformin transporters OCT1 and MATE1, respectively. The function of a gene variant near ATM gene identified by a genome-wide association study is not elucidated so far. The first variant associated with the response to gliptins is a polymorphism in the proximity of CTRB1/2 gene which encodes chymotrypsinogen. Establishment of diabetes pharmacogenetics consortia and reduction in costs of genomics might lead to some significant clinical breakthroughs in this field in a near future.