Genetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative review

Abstract Background Organic cation transporter 2 (OCT2) is a renal carrier transporter protein found in the basolateral membrane of proximal epithelial cells, which facilitates active secretion of Metformin. The genetic polymorphism of OCT2 influences the pharmacodynamic and pharmacokinetic effect o...

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Main Authors: Swathi Swaroopa Borra, Niva Rose Jane, Dhivyaprasath Palaniappan, Rupakrishnan Subramanian, Mithila Amar Patankar, Sadagoban Gopal Krishnamoorthy, Arun Kanniyappan Parthasarathy
Format: Article
Language:English
Published: SpringerOpen 2023-01-01
Series:Egyptian Journal of Medical Human Genetics
Subjects:
Online Access:https://doi.org/10.1186/s43042-023-00388-z
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author Swathi Swaroopa Borra
Niva Rose Jane
Dhivyaprasath Palaniappan
Rupakrishnan Subramanian
Mithila Amar Patankar
Sadagoban Gopal Krishnamoorthy
Arun Kanniyappan Parthasarathy
author_facet Swathi Swaroopa Borra
Niva Rose Jane
Dhivyaprasath Palaniappan
Rupakrishnan Subramanian
Mithila Amar Patankar
Sadagoban Gopal Krishnamoorthy
Arun Kanniyappan Parthasarathy
author_sort Swathi Swaroopa Borra
collection DOAJ
description Abstract Background Organic cation transporter 2 (OCT2) is a renal carrier transporter protein found in the basolateral membrane of proximal epithelial cells, which facilitates active secretion of Metformin. The genetic polymorphism of OCT2 influences the pharmacodynamic and pharmacokinetic effect of Metformin in type 2 diabetes mellitus (T2DM) patients. This is also mainly associated with frequencies of the associated risk allele in a particular population. Objective The purpose of the study is to determine the impact of OCT2 genetic polymorphism on Metformin pharmacodynamics (PD) and pharmacokinetics (PK). Method of study Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for performing the research. Following databases were used to conduct the search: PubMed/MEDLINE, Google Scholar, and the Cochrane Library. Relevant studies were retrieved and literatures were appraised for methodology, demographic characteristics, relevant SNPs, genetic intervention trials, and outcomes. Results Based on the data collected, 13 OCT2 Single nucleotide polymorphisms (SNPs) were identified across various ethnic groups. There were significant differences between the frequency distribution of shared alleles and impact of thirteen SNPs on Metformin. Among the thirteen OCT2 variants studied, rs316019 variant produced the most diverse responses in population by showing positive and negative impact on PK & PD of Metformin. Discussion and conclusion Each population's OCT2 polymorphism had a distinct effect on Metformin responsiveness. The findings of this study could bring significant benefits to patients with OCT2 genetic polymorphism if individualised T2DM therapy is introduced. Patient-centered treatment would improve the Metformin efficacy leading to new research in personalised medicine.
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spelling doaj.art-eec71801638b4d83a62fd429a0104aaf2023-01-29T12:14:04ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412023-01-012411910.1186/s43042-023-00388-zGenetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative reviewSwathi Swaroopa Borra0Niva Rose Jane1Dhivyaprasath Palaniappan2Rupakrishnan Subramanian3Mithila Amar Patankar4Sadagoban Gopal Krishnamoorthy5Arun Kanniyappan Parthasarathy6Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and ResearchDepartment of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and ResearchDepartment of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and ResearchDepartment of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and ResearchDepartment of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and ResearchDepartment of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and ResearchDepartment of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and ResearchAbstract Background Organic cation transporter 2 (OCT2) is a renal carrier transporter protein found in the basolateral membrane of proximal epithelial cells, which facilitates active secretion of Metformin. The genetic polymorphism of OCT2 influences the pharmacodynamic and pharmacokinetic effect of Metformin in type 2 diabetes mellitus (T2DM) patients. This is also mainly associated with frequencies of the associated risk allele in a particular population. Objective The purpose of the study is to determine the impact of OCT2 genetic polymorphism on Metformin pharmacodynamics (PD) and pharmacokinetics (PK). Method of study Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for performing the research. Following databases were used to conduct the search: PubMed/MEDLINE, Google Scholar, and the Cochrane Library. Relevant studies were retrieved and literatures were appraised for methodology, demographic characteristics, relevant SNPs, genetic intervention trials, and outcomes. Results Based on the data collected, 13 OCT2 Single nucleotide polymorphisms (SNPs) were identified across various ethnic groups. There were significant differences between the frequency distribution of shared alleles and impact of thirteen SNPs on Metformin. Among the thirteen OCT2 variants studied, rs316019 variant produced the most diverse responses in population by showing positive and negative impact on PK & PD of Metformin. Discussion and conclusion Each population's OCT2 polymorphism had a distinct effect on Metformin responsiveness. The findings of this study could bring significant benefits to patients with OCT2 genetic polymorphism if individualised T2DM therapy is introduced. Patient-centered treatment would improve the Metformin efficacy leading to new research in personalised medicine.https://doi.org/10.1186/s43042-023-00388-zGenetic polymorphismOCT2SLC22A2Substrate drugsMetforminType 2 diabetes mellitus (T2DM)
spellingShingle Swathi Swaroopa Borra
Niva Rose Jane
Dhivyaprasath Palaniappan
Rupakrishnan Subramanian
Mithila Amar Patankar
Sadagoban Gopal Krishnamoorthy
Arun Kanniyappan Parthasarathy
Genetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative review
Egyptian Journal of Medical Human Genetics
Genetic polymorphism
OCT2
SLC22A2
Substrate drugs
Metformin
Type 2 diabetes mellitus (T2DM)
title Genetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative review
title_full Genetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative review
title_fullStr Genetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative review
title_full_unstemmed Genetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative review
title_short Genetic polymorphism of organic cation transporter 2 (OCT2) and its effects on the pharmacokinetics and pharmacodynamics of Metformin: a narrative review
title_sort genetic polymorphism of organic cation transporter 2 oct2 and its effects on the pharmacokinetics and pharmacodynamics of metformin a narrative review
topic Genetic polymorphism
OCT2
SLC22A2
Substrate drugs
Metformin
Type 2 diabetes mellitus (T2DM)
url https://doi.org/10.1186/s43042-023-00388-z
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