Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus

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, Hugo A. Barrera-Saldaña

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number320
JournalFrontiers in Pharmacology
Volume9
Issue numberAPR
DOIs
Publication statusPublished - 6 Apr 2018

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus'. Together they form a unique fingerprint.

  • Activities

    • 1 Consultancy

    Pharmacogenetics of type 2 Diabetes Mellitus

    Rafael Baltazar Reyes León Cachón (Consultant)

    17 Jun 201417 Jun 2015

    Activity: Consultancy typesConsultancy

    Cite this

    Sanchez-Ibarra, H. E., Reyes-Cortes, L. M., Jiang, X. L., Luna-Aguirre, C. M., Aguirre-Trevino, D., Morales-Alvarado, I. A., Leon-Cachon, R. B., Lavalle-Gonzalez, F., Morcos, F., & Barrera-Saldaña, H. A. (2018). Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus. Frontiers in Pharmacology, 9(APR), [320]. https://doi.org/10.3389/fphar.2018.00320