Longitudinal assessment of SNPs rs72552763 and rs622342 in SLC22A1 over HbA1c control among Mexican-Mestizo diabetic type 2 patients
In Mexico, 75% of diabetes mellitus type 2 (DMT2) patients are not in glycaemic control criteria (HbA1c<7%); this entails a significantly variable drug response. Amongst the factors influencing such variability, are genetics, more specifically, single nucleotide polymorphisms (SNPs). Three genes...
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Published in | Frontiers in pharmacology Vol. 15; p. 1433519 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
30.09.2024
|
Subjects | |
Online Access | Get full text |
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Summary: | In Mexico, 75% of diabetes mellitus type 2 (DMT2) patients are not in glycaemic control criteria (HbA1c<7%); this entails a significantly variable drug response. Amongst the factors influencing such variability, are genetics, more specifically, single nucleotide polymorphisms (SNPs). Three genes implied in metformin pharmacokinetics are
,
, and
, which are polymorphic. While there have been cross-sectional studies on their SNPs impact over drug response, a longitudinal study would contribute valuable information on their effect over time.
SNPs of
(rs72552763, rs622342, rs12208357, rs2282143, rs594709, rs628031, and rs683369),
(rs316019), and
(rs2076828), 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% (time 0) was considered as an inescapable inclusion criterion. The study's cases were those patients who reported HbA1c ≥ 7% (time1) after time 0 (t0). Kaplan-Meier curves including a Log-Rank test and a Cox multivariate analysis of proportional risks were performed.
Determining clinical, biochemical, and genetic variables which may affect non-control (HbA1c ≥ 7%) survival time spans amongst DMT2 Mexican-Mestizo patients undergoing metformin monotherapy at
(HRAEI) between October 2013 and December 2023.
All 69 patients were monitored over a median period of 642 days (273-1,134). A comparison between time 0 and time 1 (t1) revealed differences in weight (
= 0.036), metformin dose mg/kg/day (
= 0.003), plasmatic glucose mg/dL (
= 0.048), and HbA1c (
< 0.001). The median non-control survival rate was different across the 3 genotypes of rs62552763 in
(
= 0.0034) and the dominant genotypic model GAT/GAT vs. GAT/del + del/del (
= 0.009). There were differences between rs622342 genotypes as well (
= 0.041). In GAT/GAT the Cox model found HR = 0.407 (IC95%: 0.202-0.818,
= 0.011) in the univariate analysis and HR = 0.418 (IC95%: 0.204-0.856,
= 0.034) in the multivariate analysis, adjusted by initial metformin dose (mg/kg/day), initial weight (kg), and final metformin dose (mg/kg/day). Genotype A/A of rs622342 in
, reported HR = 0.392 (IC95%: 0.169-0.910,
= 0.029) in the multivariate analysis as well.
Among DMT2 Mexican-Mestizo patients undergoing metformin monotherapy the minor allele del in rs72552763 and the minor allele C in rs622342 reported a significantly shorter survival median respect to the wild type variant. Patients carrying del in rs72552763 or C in rs622342, both in
, will reach non-control in less time with respect to other patients. Therefore these genotypes may constitute a therapeutic response biomarker for this population. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Georgia Ragia, Democritus University of Thrace, Greece ORCID: Adiel Ortega-Ayala, orcid.org/0000-0003-1300-5364, Fernando De Andrés, orcid.org/0000-0000-0003-1076-0743 Rocio Gomez, Center for Research and Advanced Studies (CINVESTAV), Mexico Edited by: Vijay Suppiah, University of South Australia, Australia |
ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2024.1433519 |