Sulfonylurea Pharmacogenomics in Type 2 Diabetes: the Influence of Drug Target and Diabetes Risk Polymorphisms

Overview

Journal Expert Rev Cardiovasc Ther

Specialty Cardiology & Vascular Diseases

Date 2010 Mar 13

PMID 20222815

Citations 38

Authors

Christina L Aquilante

Affiliations

Soon will be listed here.

Abstract

The sulfonylureas stimulate insulin release from pancreatic beta cells, and have been a cornerstone of Type 2 diabetes pharmacotherapy for over 50 years. Although sulfonylureas are effective antihyperglycemic agents, interindividual variability exists in drug response (i.e., pharmacodynamics), disposition (i.e., pharmacokinetics) and adverse effects. The field of pharmacogenomics has been applied to sulfonylurea clinical studies in order to elucidate the genetic underpinnings of this response variability. Historically, most studies have sought to determine the influence of polymorphisms in drug-metabolizing enzyme genes on sulfonylurea pharmacokinetics in humans. More recently, polymorphisms in sulfonylurea drug target genes and diabetes risk genes have been implicated as important determinants of sulfonylurea pharmacodynamics in patients with Type 2 diabetes. As such, the purpose of this review is to discuss sulfonylurea pharmacogenomics in the setting of Type 2 diabetes, specifically focusing on polymorphisms in drug target and diabetes risk genes, and their relationship with interindividual variability in sulfonylurea response and adverse effects.

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References

Holstein A, Hahn M, Stumvoll M, Kovacs P . The E23K variant of KCNJ11 and the risk for severe sulfonylurea-induced hypoglycemia in patients with type 2 diabetes. Horm Metab Res. 2009; 41(5):387-90. DOI: 10.1055/s-0029-1192019. View

Grant R, Moore A, Florez J . Genetic architecture of type 2 diabetes: recent progress and clinical implications. Diabetes Care. 2009; 32(6):1107-14. PMC: 2681026. DOI: 10.2337/dc08-2171. View

Ray K, Seshasai S, Wijesuriya S, Sivakumaran R, Nethercott S, Preiss D . Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009; 373(9677):1765-72. DOI: 10.1016/S0140-6736(09)60697-8. View

Pearson E . Translating TCF7L2: from gene to function. Diabetologia. 2009; 52(7):1227-30. DOI: 10.1007/s00125-009-1356-1. View

Kelly T, Bazzano L, Fonseca V, Thethi T, Reynolds K, He J . Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med. 2009; 151(6):394-403. DOI: 10.7326/0003-4819-151-6-200909150-00137. View

Hamming K, Soliman D, Matemisz L, Niazi O, Lang Y, Gloyn A . Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel. Diabetes. 2009; 58(10):2419-24. PMC: 2750221. DOI: 10.2337/db09-0143. View

Zhou K, Donnelly L, Burch L, Tavendale R, Doney A, Leese G . Loss-of-function CYP2C9 variants improve therapeutic response to sulfonylureas in type 2 diabetes: a Go-DARTS study. Clin Pharmacol Ther. 2009; 87(1):52-6. DOI: 10.1038/clpt.2009.176. View

Schwanstecher C, Meyer U, Schwanstecher M . K(IR)6.2 polymorphism predisposes to type 2 diabetes by inducing overactivity of pancreatic beta-cell ATP-sensitive K(+) channels. Diabetes. 2002; 51(3):875-9. DOI: 10.2337/diabetes.51.3.875. View

Kirchheiner J, Bauer S, Meineke I, Rohde W, Prang V, Meisel C . Impact of CYP2C9 and CYP2C19 polymorphisms on tolbutamide kinetics and the insulin and glucose response in healthy volunteers. Pharmacogenetics. 2002; 12(2):101-9. DOI: 10.1097/00008571-200203000-00004. View

10.

Reis A, Velho G . Sulfonylurea receptor -1 (SUR1): genetic and metabolic evidences for a role in the susceptibility to type 2 diabetes mellitus. Diabetes Metab. 2002; 28(1):14-9. View

11.

Kirchheiner J, Brockmoller J, Meineke I, Bauer S, Rohde W, Meisel C . Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clin Pharmacol Ther. 2002; 71(4):286-96. DOI: 10.1067/mcp.2002.122476. View

12.

Marchetti P, Lupi R, Federici M, Marselli L, Masini M, Boggi U . Insulin secretory function is impaired in isolated human islets carrying the Gly(972)-->Arg IRS-1 polymorphism. Diabetes. 2002; 51(5):1419-24. DOI: 10.2337/diabetes.51.5.1419. View

13.

Zychma M, Gumprecht J, Strojek K, Grzeszczak W, Moczulski D, Trautsolt W . Sulfonylurea receptor gene 16-3 polymorphism - association with sulfonylurea or insulin treatment in type 2 diabetic subjects. Med Sci Monit. 2002; 8(7):CR512-5. View

14.

Nielsen E, Hansen L, Carstensen B, Echwald S, Drivsholm T, Glumer C . The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes. 2003; 52(2):573-7. DOI: 10.2337/diabetes.52.2.573. View

15.

Jellema A, Zeegers M, Feskens E, Dagnelie P, Mensink R . Gly972Arg variant in the insulin receptor substrate-1 gene and association with Type 2 diabetes: a meta-analysis of 27 studies. Diabetologia. 2003; 46(7):990-5. DOI: 10.1007/s00125-003-1126-4. View

16.

Pearson E, Starkey B, Powell R, Gribble F, Clark P, Hattersley A . Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet. 2003; 362(9392):1275-81. DOI: 10.1016/S0140-6736(03)14571-0. View

17.

Stevens R, Coleman R, Adler A, Stratton I, Matthews D, Holman R . Risk factors for myocardial infarction case fatality and stroke case fatality in type 2 diabetes: UKPDS 66. Diabetes Care. 2003; 27(1):201-7. DOI: 10.2337/diacare.27.1.201. View

18.

Barroso I, Luan J, Middelberg R, Harding A, Franks P, Jakes R . Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. PLoS Biol. 2003; 1(1):E20. PMC: 212698. DOI: 10.1371/journal.pbio.0000020. View

19.

Florez J, Burtt N, de Bakker P, Almgren P, Tuomi T, Holmkvist J . Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes. 2004; 53(5):1360-8. DOI: 10.2337/diabetes.53.5.1360. View

20.

Sesti G, Marini M, Cardellini M, Sciacqua A, Frontoni S, Andreozzi F . The Arg972 variant in insulin receptor substrate-1 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes. Diabetes Care. 2004; 27(6):1394-8. DOI: 10.2337/diacare.27.6.1394. View