Pharmacogenetics of oral antidiabetic drugs

Matthijs L. Becker, Ewan R. Pearson, Ivan Tkáč

    Research output: Contribution to journalReview article

    29 Citations (Scopus)
    125 Downloads (Pure)

    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.

    Original languageEnglish
    Article number686315
    Number of pages10
    JournalInternational Journal of Endocrinology
    Volume2013
    DOIs
    Publication statusPublished - 2013

    Fingerprint Dive into the research topics of 'Pharmacogenetics of oral antidiabetic drugs'. Together they form a unique fingerprint.

    Cite this