Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients with Type 2 Diabetes Mellitus

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dc.contributor.authorSanchez-Ibarra, Hector E.
dc.contributor.authorReyes-Cortes, Luisa M.
dc.contributor.authorJiang, Xian-Li
dc.contributor.authorLuna-Aguirre, Claudia M.
dc.contributor.authorAguirre-Trevino, Dionicio
dc.contributor.authorMorales-Alvarado, Ivan A.
dc.contributor.authorLeon-Cachon, Rafael B.
dc.contributor.authorLavalle-Gonzalez, Fernando
dc.contributor.authorMorcos, Faruck
dc.contributor.authorBarrera-Saldana, Hugo A.
dc.contributor.utdAuthorJiang, Xian-Li
dc.contributor.utdAuthorMorcos, Faruck
dc.date.accessioned2019-05-16T20:58:35Z
dc.date.available2019-05-16T20:58:35Z
dc.date.created2018-04-06
dc.description.abstractThe 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.
dc.description.departmentSchool of Natural Sciences and Mathematics
dc.description.sponsorship"This work was funded by the National Council on Science and Technology (CONACYT) (Grant Nos. 185427, ECO-2015-C01-260826, 294875, and 280114)."
dc.identifier.bibliographicCitationSanchez-Ibarra, Hector E., Luisa M. Reyes-Cortes, Xian-Li Jiang, Claudia M. Luna-Aguirre, et al. 2018. "Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes mellitus." Frontiers In Pharmacology 9: 320-1 to 11, doi:10.3389/fphar.2018.00320
dc.identifier.issn1663-9812
dc.identifier.urihttps://hdl.handle.net/10735.1/6503
dc.identifier.volume9
dc.language.isoen
dc.publisherFrontiers Media SA
dc.relation.urihttp://doi.org/10.3389/fphar.2018.00320
dc.rightsCC BY 4.0 (Attribution)
dc.rights©2018 The Authors
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.source.journalFrontiers in Pharmacology
dc.subjectAlleles
dc.subjectMetformin
dc.subjectPolymorphism, Genetic
dc.subjectHypoglycemia
dc.subjectGenes
dc.subjectGlucose
dc.subjectPharmacogenetics
dc.subjectPharmacogenomics
dc.subjectDiabetes
dc.subjectDiabetes Mellitus
dc.subjectSulfonylurea Compounds
dc.subjectSulfonylureas
dc.subjectBiguanides
dc.subjectHispanic Americans
dc.subjectGenetic polymorphisms
dc.titleGenotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients with Type 2 Diabetes Mellitus
dc.type.genrearticle

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