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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1433519

Longitudinal assessment of SNPs rs72552763 and rs622342 in SLC22A1 over HbA1c control among Mexican-Mestizo Diabetic Type 2 patients

Provisionally accepted
ADIEL ORTEGA-AYALA ADIEL ORTEGA-AYALA 1Fernando De Andrés Fernando De Andrés 2Adrián LLerena Adrián LLerena 3Carlos Miguel Bartolo-Montiel Carlos Miguel Bartolo-Montiel 4Gustavo Acosta-Altamirano Gustavo Acosta-Altamirano 5JUAN ARCADIO MOLINA-GUARNEROS JUAN ARCADIO MOLINA-GUARNEROS 1*
  • 1 Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico, Mexico
  • 2 Department Analytical Chemistry and Food Technology, Faculty of Pharmacy, University Castilla-La Mancha, Albacete, Spain
  • 3 University Institute for Bio‑sanitary Research of Extremadura, Badajoz, Spain
  • 4 Directorate of Planification, Teaching, and Research, High‑Speciality Regional Hospital of Ixtapaluca, Ixtapaluca, Mexico
  • 5 Directorate of Research, General Hospital of Mexico City, Mexico, Mexico

The final, formatted version of the article will be published soon.

    Background. In Mexico, 75% of patients are not within glycaemic control criteria (HbA1c<7%), which entails a significantly variable drug response. Amongst the factors influencing this variability, are genetics, more specifically, single nucleotide polymorphisms. Three genes implied in metformin pharmacokinetics are SLC22A1, SLC22A2, and SLC22A3, which are polymorphic. While there have been cross-sectional studies on the drug response of these genes' SNPs, a longitudinal study would contribute valuable information on their effect over time. Methods. SNPs of SLC22A1, SLC22A2, and SLC22A3, were determined through PCR-TR. The clinical records of 69 patients undergoing metformin monotherapy were retrospectively assessed, metformin is the first line treatment against DMT2. A level of HbA1c<7% (time0) was considered as an inescapable inclusion criterion. Our cases were those patients who achieved HbA1c ≥7% (time1) during that period. Kaplan-Meier curves with Log-Rank test and a Cox multivariate analysis of proportional risks were performed. Aim. Determining clinical, biochemical, and genetic variables which may affect non-control (HbA1c≥7%) survival time spans amongst DT2 Mexican-Mestizo patients undergoing metformin monotherapy at HRAEI between October 2013 and December 2023. Results. 69 patients were monitored over a median period of 642 days . A comparison between time0 and time1 revealed differences in weight (p= 0.036), metformin dose mg/kg/day (p=0.003), plasmatic glucose mg/dl (p=0.048), and HbA1c (p<0.001). The median non-control survival rate was different across the 3 genotypes of rs72552763 (p=0.0034) and the dominant genotypic model GAT/GAT vs GAT/del+del/del (p=0.009). There were differences between rs622342 genotypes as well (p=0.041). In GAT/GAT the Cox model found HR=0.407 (IC95%:0.202-0.818, p=0.011) in the univariate analysis and HR=0.418 (IC95%:0.204-0.856, p=0.034) in the multivariate analysis. A/A in rs622342, reported HR=0.392 (IC95%: 0.169-0.910, p=0.029) in the multivariate analysis as well. Conclusions. Amongst DT2 Mexican-Mestizo patients undergoing metformin monotherapy the minor allele del in rs72552763 and the minor allele C in rs622342 report a significantly shorter survival median respect to the wild type variant. Patients carrying del in rs72552763 or C in rs622342 will reach non-control in less time with respect to other patients. Therefore these genotypes may constitute a therapeutic response biomarker for this population.

    Keywords: rs72552763, rs622342, HbA1c control, Metformin, Diabetes T2

    Received: 24 May 2024; Accepted: 21 Aug 2024.

    Copyright: © 2024 ORTEGA-AYALA, De Andrés, LLerena, Bartolo-Montiel, Acosta-Altamirano and MOLINA-GUARNEROS. 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) or licensor 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.

    * Correspondence: JUAN ARCADIO MOLINA-GUARNEROS, Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico, Mexico

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