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Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels

Type 2 diabetes mellitus (T2DM) constitutes a major portion of Jordan’s disease burden, and incidence rates are rising at a rapid rate. Due to variability in the drug’s response between ethnic groups, it is imperative that the pharmacogenetics of metformin be investigated in the Jordanian population...

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Autores principales: AL-Eitan, Laith N., Almomani, Basima A., Nassar, Ahmad M., Elsaqa, Barakat Z., Saadeh, Nesreen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462993/
https://www.ncbi.nlm.nih.gov/pubmed/30934600
http://dx.doi.org/10.3390/jpm9010017
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author AL-Eitan, Laith N.
Almomani, Basima A.
Nassar, Ahmad M.
Elsaqa, Barakat Z.
Saadeh, Nesreen A.
author_facet AL-Eitan, Laith N.
Almomani, Basima A.
Nassar, Ahmad M.
Elsaqa, Barakat Z.
Saadeh, Nesreen A.
author_sort AL-Eitan, Laith N.
collection PubMed
description Type 2 diabetes mellitus (T2DM) constitutes a major portion of Jordan’s disease burden, and incidence rates are rising at a rapid rate. Due to variability in the drug’s response between ethnic groups, it is imperative that the pharmacogenetics of metformin be investigated in the Jordanian population. The objective of this study was to investigate the relationship between twenty-one single nucleotide polymorphisms (SNPs) in the SLC22A1, SLC22A2, and SLC22A3 genes and their effects on metformin pharmacogenetics in Jordanian patients diagnosed with type 2 diabetes mellitus. Blood samples were collected from 212 Jordanian diabetics who fulfilled the inclusion criteria, which were then used in SNP genotyping and determination of HbA1c levels. The rs12194182 SNP in the SLC22A3 gene was found to have a significant association (p < 0.05) with lower mean HbA1c levels, and this association more pronounced in patients with the CC genotype (i.e., p-value was significant before correcting for multiple testing). Moreover, the multinomial logistic regression analysis showed that SNP genotypes within the SLC22A1, SLC22A2, and SLC22A3 genes, body mass index (BMI) and age of diagnosis were significantly associated with glycemic control (p < 0.05). The results of this study can be used to predict response to metformin and other classes of T2DM drugs, making treatment more individualized and resulting in better clinical outcomes.
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spelling pubmed-64629932019-04-19 Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels AL-Eitan, Laith N. Almomani, Basima A. Nassar, Ahmad M. Elsaqa, Barakat Z. Saadeh, Nesreen A. J Pers Med Article Type 2 diabetes mellitus (T2DM) constitutes a major portion of Jordan’s disease burden, and incidence rates are rising at a rapid rate. Due to variability in the drug’s response between ethnic groups, it is imperative that the pharmacogenetics of metformin be investigated in the Jordanian population. The objective of this study was to investigate the relationship between twenty-one single nucleotide polymorphisms (SNPs) in the SLC22A1, SLC22A2, and SLC22A3 genes and their effects on metformin pharmacogenetics in Jordanian patients diagnosed with type 2 diabetes mellitus. Blood samples were collected from 212 Jordanian diabetics who fulfilled the inclusion criteria, which were then used in SNP genotyping and determination of HbA1c levels. The rs12194182 SNP in the SLC22A3 gene was found to have a significant association (p < 0.05) with lower mean HbA1c levels, and this association more pronounced in patients with the CC genotype (i.e., p-value was significant before correcting for multiple testing). Moreover, the multinomial logistic regression analysis showed that SNP genotypes within the SLC22A1, SLC22A2, and SLC22A3 genes, body mass index (BMI) and age of diagnosis were significantly associated with glycemic control (p < 0.05). The results of this study can be used to predict response to metformin and other classes of T2DM drugs, making treatment more individualized and resulting in better clinical outcomes. MDPI 2019-03-25 /pmc/articles/PMC6462993/ /pubmed/30934600 http://dx.doi.org/10.3390/jpm9010017 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
AL-Eitan, Laith N.
Almomani, Basima A.
Nassar, Ahmad M.
Elsaqa, Barakat Z.
Saadeh, Nesreen A.
Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels
title Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels
title_full Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels
title_fullStr Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels
title_full_unstemmed Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels
title_short Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels
title_sort metformin pharmacogenetics: effects of slc22a1, slc22a2, and slc22a3 polymorphisms on glycemic control and hba1c levels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462993/
https://www.ncbi.nlm.nih.gov/pubmed/30934600
http://dx.doi.org/10.3390/jpm9010017
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