title: Pharmacogenetics of oral antidiabetic treatment.
abstract: In the majority of patients with type 2 diabetes (T2D), oral antidiabetic drug (OAD) treatment is the first line treatment after lifestyle measures fail. Two major groups of OAD are used in clinical practice--insulin secretagogues and insulin sensitisers. Sulphonyluea (SU) derivatives are insulin secretagogues and stimulate insulin secretion by inhibiting ATP-sensitive potassium channels. Genes KCNJ11 and ABCC8 encode potassium channel proteins. KCNJ11 gene Glu23Lys polymorphism was associated with an increased risk of SU secondary failure, while Ser1369Ala polymorphism of ABCC8 gene had influence antidiabetic efficacy of SU drug gliclazide. In addition, the polymorphism of TCF7L2 gene, which has the strongest association with T2D, also influenced secondary SU drug failure. Insulin sensitisers include both metformin and glitazones. Some drug-genotype associations were observed for metformin in patients with T2D. Several genes influenced the effect of glitazone treatment. Rosiglitazone was more effective in diabetes control in carriers of Prol2Ala polymorphism of PPARG gene encoding the PPARg-receptor--the target of this drug. Rosiglitazone treatment had less effect on glycemic control and adiponectin increase in T2D patients with GG-genotypes of adiponectin (APM1) polymorphism. Pioglitazone treatment had smaller effect on glycemic control in patients with LPL Ser447X polymorphism. Identification of drug-genotype interactions in pharmacogenetic studies of the OAD treatment might have clinical implications in the near future resulting in selection of more specific "patient-tailored therapy" in T2D (Tab. 1, Ref. 58).
authors.affiliation: Department of Internal Medicine 4, Center of Excellence for the Study of Atherosclerosis, Faculty of Medicine, Safarik University, Kosice, Slovakia. zbynek.schroner@gmail.com
authors.forename: Z
authors.initials: Z
authors.lastname: Schroner
authors.forename: M
authors.initials: M
authors.lastname: Javorsky
authors.forename: M
authors.initials: M
authors.lastname: Kozarova
authors.forename: I
authors.initials: I
authors.lastname: Tkac
mesh_terms: D000284:Administration, Oral; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D010597:Pharmacogenetics
chemical_list: D007004:Hypoglycemic Agents