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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 10, 2016; 7(15): 302-315
Published online Aug 10, 2016. doi: 10.4239/wjd.v7.i15.302
Pharmacogenetic studies update in type 2 diabetes mellitus
Shalini Singh, Kauser Usman, Monisha Banerjee
Shalini Singh, Monisha Banerjee, Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow 226007, India
Kauser Usman, Department of Medicine, King George’s Medical University, Lucknow 226003, India
Author contributions: All authors contributed to this manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Monisha Banerjee, Professor, Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, University Road, Lucknow 226007, India. banerjee_monisha30@rediffmail.com
Telephone: +91-98-39500439
Received: March 29, 2016
Peer-review started: March 31, 2016
First decision: May 17, 2016
Revised: May 30, 2016
Accepted: June 27, 2016
Article in press: June 29, 2016
Published online: August 10, 2016
Processing time: 133 Days and 8.9 Hours
Abstract

Type 2 diabetes mellitus (T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs (OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.

Keywords: Type 2 diabetes mellitus; Pharmacogenetics; Genetic variants; Oral antidiabetic drugs; Personalized medicine

Core tip: Type 2 diabetes mellitus (T2DM) is a highly prevalent metabolic disorder, characterized by chronic hyperglycemia. It results from an interaction of environmental as well as genetic factors. Several genes have been identified associated with disease development and therapeutic outcomes. Inter-individual variations in the human genome affect both, risk of T2DM development and personalized response to identical drug therapies. Pharmacogenetic approaches focus on single nucleotide polymorphisms and their influence on individual drug response, efficacy and toxicity. In the present study, an effort has been made to review the genetic polymorphisms in candidate genes associated with efficacy of oral antidiabetic drugs.