Open Access

Frequency of CYP2C9 (*2, *3 and IVS8‑109A>T) allelic variants, and their clinical implications, among Mexican patients with diabetes mellitus type 2 undergoing treatment with glibenclamide and metformin

  • Authors:
    • Patricia Cuautle‑Rodríguez
    • Nidia Rodríguez‑Rivera
    • Fernando De Andrés
    • Fernando Castillo‑Nájera
    • Adrián Llerena
    • Juan Arcadio Molina‑Guarneros
  • View Affiliations

  • Published online on: April 4, 2019     https://doi.org/10.3892/br.2019.1204
  • Pages: 283-295
  • Copyright: © Cuautle‑Rodríguez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The majority of Mexican patients with diabetes mellitus type 2 (DMT2) (67.9‑85.0%) are prescribed sulphonylureas (SUs), which are metabolized by cytochrome P450 2C9 (abbreviated as CYP2C9). SUs are a type of oral anti‑diabetic compound which inhibit ATP‑sensitive potassium channels, thus inducing glucose‑independent insulin release by the β‑pancreatic cells. The wide variability reported in SU responses has been attributed to the polymorphisms of CYP2C9. The present study aimed to describe CYP2C9 polymorphisms (*2, *3 and IVS8‑109T) within a sample of Mexican patients with DMT2, while suggesting the potential clinical implications in terms of glibenclamide response variability. From a sample of 248 patients with DMT2 who initially consented to be studied, those ultimately included in the study were treated with glibenclamide (n=11), glibenclamide combined with metformin (n=112) or metformin (n=76), and were subsequently genotyped using a reverse transcription‑quantitative polymerase chain reaction (PCR), end‑point allelic discrimination and PCR amplifying enzymatic restriction fragment long polymorphism. Clinical data were gathered through medical record revision. The frequencies revealed were as follows: CYP2C9*1/*1, 87.5%; *1/*2, 6.5%; *1/*3, 5.2%; and CYP2C9, IVS8‑109A>T, 16.1%. Glibenclamide significantly reduced the level of pre‑prandial glucose (P<0.01) and the percentage of glycated hemoglobin (%HbA1c; P<0.01) for IVS8‑109A>T compared with combined glibenclamide and metformin treatment. Concerning the various treatments with respect to the different genotypes, the percentages obtained were as follows: Glibenclamide A/A, HbA1c<6.5=33.3%; glibenclamide + metformin A/A, HbA1c<6.5=24.6%; glibenclamide A/T, HbA1c<6.5=33.3%; glibenclamide + metformin A/T, HbA1c<6.5=25%; glibenclamide T/T, HbA1c<6.5=100%; and glibenclamide + metformin T/T, HbA1c<6.5=12.5%. Altogether, these results revealed that, although genetically customized prescriptions remain a desirable goal to increase the chances of therapeutic success, within the studied population neither allelic variants nor dosages demonstrated a clear association with biomarker levels. A key limitation of the present study was the lack of ability to quantify either the plasma concentrations of SU or their metabolites; therefore, further, precise experimental and observational studies are required.

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APA
Cuautle‑Rodríguez, P., Rodríguez‑Rivera, N., De Andrés, F., Castillo‑Nájera, F., Llerena, A., & Molina‑Guarneros, J.A. (2019). Frequency of CYP2C9 (*2, *3 and IVS8‑109A>T) allelic variants, and their clinical implications, among Mexican patients with diabetes mellitus type 2 undergoing treatment with glibenclamide and metformin. Biomedical Reports, 10, 283-295. https://doi.org/10.3892/br.2019.1204
MLA
Cuautle‑Rodríguez, P., Rodríguez‑Rivera, N., De Andrés, F., Castillo‑Nájera, F., Llerena, A., Molina‑Guarneros, J. A."Frequency of CYP2C9 (*2, *3 and IVS8‑109A>T) allelic variants, and their clinical implications, among Mexican patients with diabetes mellitus type 2 undergoing treatment with glibenclamide and metformin". Biomedical Reports 10.5 (2019): 283-295.
Chicago
Cuautle‑Rodríguez, P., Rodríguez‑Rivera, N., De Andrés, F., Castillo‑Nájera, F., Llerena, A., Molina‑Guarneros, J. A."Frequency of CYP2C9 (*2, *3 and IVS8‑109A>T) allelic variants, and their clinical implications, among Mexican patients with diabetes mellitus type 2 undergoing treatment with glibenclamide and metformin". Biomedical Reports 10, no. 5 (2019): 283-295. https://doi.org/10.3892/br.2019.1204