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Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus
The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others. The marked inter-individual differences among T2DM patients’ res...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898372/ https://www.ncbi.nlm.nih.gov/pubmed/29681852 http://dx.doi.org/10.3389/fphar.2018.00320 |
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author | Sanchez-Ibarra, Hector E. Reyes-Cortes, Luisa M. Jiang, Xian-Li Luna-Aguirre, Claudia M. Aguirre-Trevino, Dionicio Morales-Alvarado, Ivan A. Leon-Cachon, Rafael B. Lavalle-Gonzalez, Fernando Morcos, Faruck Barrera-Saldaña, Hugo A. |
author_facet | Sanchez-Ibarra, Hector E. Reyes-Cortes, Luisa M. Jiang, Xian-Li Luna-Aguirre, Claudia M. Aguirre-Trevino, Dionicio Morales-Alvarado, Ivan A. Leon-Cachon, Rafael B. Lavalle-Gonzalez, Fernando Morcos, Faruck Barrera-Saldaña, Hugo A. |
author_sort | Sanchez-Ibarra, Hector E. |
collection | PubMed |
description | The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others. The marked inter-individual differences among T2DM patients’ response to these drugs have become an issue on prescribing and dosing efficiently. In this study, fourteen polymorphisms selected from Genome-wide association studies (GWAS) were screened in 495 T2DM Mexican patients previously treated with OADs to find the relationship between the presence of these polymorphisms and response to the OADs. Then, a novel association screening method, based on global probabilities, was used to globally characterize important relationships between the drug response to OADs and genetic and clinical parameters, including polymorphisms, patient information, and type of treatment. Two polymorphisms, ABCC8-Ala1369Ser and KCNJ11-Glu23Lys, showed a significant impact on response to SUs. Heterozygous ABCC8-Ala1369Ser variant (A/C) carriers exhibited a higher response to SUs compared to homozygous ABCC8-Ala1369Ser variant (A/A) carriers (p-value = 0.029) and to homozygous wild-type genotypes (C/C) (p-value = 0.012). The homozygous KCNJ11-Glu23Lys variant (C/C) and wild-type (T/T) genotypes had a lower response to SUs compared to heterozygous (C/T) carriers (p-value = 0.039). The screening of OADs response related genetic and clinical factors could help improve the prescribing and dosing of OADs for T2DM patients and thus contribute to the design of personalized treatments. |
format | Online Article Text |
id | pubmed-5898372 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58983722018-04-20 Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus Sanchez-Ibarra, Hector E. Reyes-Cortes, Luisa M. Jiang, Xian-Li Luna-Aguirre, Claudia M. Aguirre-Trevino, Dionicio Morales-Alvarado, Ivan A. Leon-Cachon, Rafael B. Lavalle-Gonzalez, Fernando Morcos, Faruck Barrera-Saldaña, Hugo A. Front Pharmacol Pharmacology The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others. The marked inter-individual differences among T2DM patients’ response to these drugs have become an issue on prescribing and dosing efficiently. In this study, fourteen polymorphisms selected from Genome-wide association studies (GWAS) were screened in 495 T2DM Mexican patients previously treated with OADs to find the relationship between the presence of these polymorphisms and response to the OADs. Then, a novel association screening method, based on global probabilities, was used to globally characterize important relationships between the drug response to OADs and genetic and clinical parameters, including polymorphisms, patient information, and type of treatment. Two polymorphisms, ABCC8-Ala1369Ser and KCNJ11-Glu23Lys, showed a significant impact on response to SUs. Heterozygous ABCC8-Ala1369Ser variant (A/C) carriers exhibited a higher response to SUs compared to homozygous ABCC8-Ala1369Ser variant (A/A) carriers (p-value = 0.029) and to homozygous wild-type genotypes (C/C) (p-value = 0.012). The homozygous KCNJ11-Glu23Lys variant (C/C) and wild-type (T/T) genotypes had a lower response to SUs compared to heterozygous (C/T) carriers (p-value = 0.039). The screening of OADs response related genetic and clinical factors could help improve the prescribing and dosing of OADs for T2DM patients and thus contribute to the design of personalized treatments. Frontiers Media S.A. 2018-04-06 /pmc/articles/PMC5898372/ /pubmed/29681852 http://dx.doi.org/10.3389/fphar.2018.00320 Text en Copyright © 2018 Sanchez-Ibarra, Reyes-Cortes, Jiang, Luna-Aguirre, Aguirre-Trevino, Morales-Alvarado, Leon-Cachon, Lavalle-Gonzalez, Morcos and Barrera-Saldaña. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Sanchez-Ibarra, Hector E. Reyes-Cortes, Luisa M. Jiang, Xian-Li Luna-Aguirre, Claudia M. Aguirre-Trevino, Dionicio Morales-Alvarado, Ivan A. Leon-Cachon, Rafael B. Lavalle-Gonzalez, Fernando Morcos, Faruck Barrera-Saldaña, Hugo A. Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus |
title | Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus |
title_full | Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus |
title_fullStr | Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus |
title_full_unstemmed | Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus |
title_short | Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus |
title_sort | genotypic and phenotypic factors influencing drug response in mexican patients with type 2 diabetes mellitus |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898372/ https://www.ncbi.nlm.nih.gov/pubmed/29681852 http://dx.doi.org/10.3389/fphar.2018.00320 |
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