Acta Pharmaceutica, Vol. 60 No. 4, 2010.
Review article
https://doi.org/10.2478/v10007-010-0040-9
Genetic polymorphisms in diabetes: Influence on therapy with oral antidiabetics
UNA GLAMOČLIJA
orcid.org/0000-0003-1206-6990
; Hercegovinalijek d.o.o., 88000 Mostar, Bosnia and Herzegovina
ADLIJA JEVRIĆ-ČAUŠEVIĆ
; Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy,University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina
Abstract
Due to new genetic insights, etiologic classification of diabetes is under constant scrutiny. Hundreds, or even thousands, of genes are linked with type 2 diabetes. Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to be predisposed to type 2 diabetes mellitus across many large studies. Individually, each of these polymorphisms is only moderately predisposed to type 2 diabetes. On the other hand, monogenic forms of diabetes such as MODY and neonatal diabetes are characterized by unique clinical features and the possibility of applying a tailored treatment.
Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets have been linked to interindividual differences in the efficacy and toxicity of a number of medications. Mutations in genes important in drug absorption, distribution, metabolism and excretion (ADME) play a critical role in pharmacogenetics of diabetes.
There are currently five major classes of oral pharmacological agents available to treat type 2 diabetes: sulfonylureas, meglitinides, metformin (a biguanide), thiazolidinediones, and α-glucosidase inhibitors. Other classes are also mentioned in literature.
In this work, different types of genetic mutations (mutations of the gene for glucokinase, HNF 1, HNF1ß and Kir6.2 and SUR1 subunit of KATP channel, PPAR-γ, OCT1 and OCT2, cytochromes, direct drug-receptor (KCNJ11), as well as the factors that influence the development of the disease (TCF7L2) and variants of genes that lead to hepatosteatosis caused by thiazolidinediones) and their influence on the response to therapy with oral antidiabetics will be reviewed.
Keywords
pharmacogenetics; oral antidiabetics
Hrčak ID:
60285
URI
Publication date:
1.12.2010.
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