Sulfonylurea pharmacogenomics in Type 2 diabetes: the influence of drug target and diabetes risk polymorphisms.
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.
Aquilante
Christina L
CL
School of Pharmacy, Department of Pharmaceutical Sciences, University of Colorado-Denver, 12700 East 19th Avenue, Aurora, CO 80045, USA. christina.aquilante@ucdenver.edu
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001786:Blood Glucose / Q000187:drug effects* / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011379:Prognosis; D013453:Sulfonylurea Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D013453:Sulfonylurea Compounds; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases