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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2018.00320/full |
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| author | Hector E. Sanchez-Ibarra Luisa M. Reyes-Cortes Xian-Li Jiang Claudia M. Luna-Aguirre Dionicio Aguirre-Trevino Ivan A. Morales-Alvarado Rafael B. Leon-Cachon Fernando Lavalle-Gonzalez Faruck Morcos Faruck Morcos Hugo A. Barrera-Saldaña Hugo A. Barrera-Saldaña |
| author_facet | Hector E. Sanchez-Ibarra Luisa M. Reyes-Cortes Xian-Li Jiang Claudia M. Luna-Aguirre Dionicio Aguirre-Trevino Ivan A. Morales-Alvarado Rafael B. Leon-Cachon Fernando Lavalle-Gonzalez Faruck Morcos Faruck Morcos Hugo A. Barrera-Saldaña Hugo A. Barrera-Saldaña |
| author_sort | Hector E. Sanchez-Ibarra |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T17:29:36Z |
| format | Article |
| id | doaj.art-e8dc387a52c344119133d7c99c2eeebd |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T17:29:36Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e8dc387a52c344119133d7c99c2eeebd2022-12-21T18:55:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-04-01910.3389/fphar.2018.00320347666Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes MellitusHector E. Sanchez-Ibarra0Luisa M. Reyes-Cortes1Xian-Li Jiang2Claudia M. Luna-Aguirre3Dionicio Aguirre-Trevino4Ivan A. Morales-Alvarado5Rafael B. Leon-Cachon6Fernando Lavalle-Gonzalez7Faruck Morcos8Faruck Morcos9Hugo A. Barrera-Saldaña10Hugo A. Barrera-Saldaña11Molecular Genetics Laboratory, Vitagénesis, S.A. de C.V., Monterrey, MexicoMolecular Genetics Laboratory, Vitagénesis, S.A. de C.V., Monterrey, MexicoEvolutionary Information Laboratory, Department of Biological Sciences, University of Texas at Dallas, Richardson, TX, United StatesMolecular Genetics Laboratory, Vitagénesis, S.A. de C.V., Monterrey, MexicoMolecular Genetics Laboratory, Vitagénesis, S.A. de C.V., Monterrey, MexicoMolecular Genetics Laboratory, Vitagénesis, S.A. de C.V., Monterrey, MexicoDepartamento de Ciencias Básicas, Centro de Diagnóstico Molecular y Medicina Personalizada, Vicerrectoría de Ciencias de la Salud, Universidad de Monterrey, Monterrey, MexicoServicio de Endocrinología, Hospital Universitario Dr. José E. González, Universidad Autónoma de Nuevo León, Monterrey, MexicoEvolutionary Information Laboratory, Department of Biological Sciences, University of Texas at Dallas, Richardson, TX, United StatesCenter for Systems Biology, University of Texas at Dallas, Richardson, TX, United StatesMolecular Genetics Laboratory, Vitagénesis, S.A. de C.V., Monterrey, MexicoTecnológico de Monterrey, Monterrey, MexicoThe 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.http://journal.frontiersin.org/article/10.3389/fphar.2018.00320/fullpharmacogeneticspharmacogenomicsdiabetessulfonylureasbiguanidesMexican |
| spellingShingle | Hector E. Sanchez-Ibarra Luisa M. Reyes-Cortes Xian-Li Jiang Claudia M. Luna-Aguirre Dionicio Aguirre-Trevino Ivan A. Morales-Alvarado Rafael B. Leon-Cachon Fernando Lavalle-Gonzalez Faruck Morcos Faruck Morcos Hugo A. Barrera-Saldaña Hugo A. Barrera-Saldaña Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus Frontiers in Pharmacology pharmacogenetics pharmacogenomics diabetes sulfonylureas biguanides Mexican |
| 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 | pharmacogenetics pharmacogenomics diabetes sulfonylureas biguanides Mexican |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2018.00320/full |
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