<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml">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 <italic>KCNJ11</italic>, Pro12 of <italic>PPARG</italic>, and the T allele at rs7903146 of <italic>TCF7L2</italic>) 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 1α, HNF1β and Kir6.2 and SUR1 subunit of KATP channel, <italic>PPAR-γ, OCT1</italic> and <italic>OCT2</italic>, cytochromes, direct drug-receptor (<italic>KCNJ11</italic>), as well as the factors that influence the development of the disease (<italic>TCF7L2</italic>) 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.</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 1α, HNF1β 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.

Genetic polymorphisms in diabetes: Influence on therapy with oral antidiabetics

Hercegovinalijek d.o.o., 88000 Mostar, Bosnia and Herzegovina

Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina

Acta Pharmaceutica

{"article-title":"Genetic polymorphisms in diabetes: Influence on therapy with oral antidiabetics"}

Due to new genetic insights, etiologic classification of diabetes is under constant scrutiny. Hundreds, or even thousands, of genes are linked with type 2...

Genetic polymorphisms in diabetes: Influence on therapy with oral antidiabetics

Pubblicato online: 17 dic 2010

Pagine: 387 - 406

DOI: https://doi.org/10.2478/v10007-010-0040-9

Parole chiave
farmakogenetika, oralni antidijabetici

This content is open access.

Genetic polymorphisms in diabetes: Influence on therapy with oral antidiabetics

Pubblicato online: 17 dic 2010

Pagine: 387 - 406

DOI: https://doi.org/10.2478/v10007-010-0040-9

Parole chiavefarmakogenetika, oralni antidijabetici

This content is open access.

Parole chiave
farmakogenetika, oralni antidijabetici