Allele frequencies and genotype distribution of three metformin transporter polymorphisms in Mexican population and their application in pharmacogenomics of type 2 diabetes

Metformin is the first-line antidiabetic therapy for type 2 diabetes in Mexico, despite recent recommendations highlighting alternatives like GLP-1 receptor agonists for individuals with obesity. Metformin elimination is reliant on liver and kidney function, and variants in transport proteins such a...

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Bibliographic Details
Published in:Frontiers in pharmacology 2024-11, Vol.15, p.1466394
Main Authors: Chávez-Arreola, Oscar I, Lazalde, Brissia, López-López, Marisol, Ortega-Vázquez, Alberto, Torres-Salazar, Quitzia L
Format: Article
Language:English
Subjects:
genotyping
MATE1
MATE2
metformin
Oct2
transporters
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Summary:Metformin is the first-line antidiabetic therapy for type 2 diabetes in Mexico, despite recent recommendations highlighting alternatives like GLP-1 receptor agonists for individuals with obesity. Metformin elimination is reliant on liver and kidney function, and variants in transport proteins such as Multidrug and Toxin Extrusion Protein 1 (MATE1), MATE2, and Organic Cation Transporter 2 (OCT2) can influence its pharmacokinetics. Understanding these variants' frequencies in the Mexican population is crucial for tailoring personalized treatment strategies. This study aimed to determine the genotypic and allelic frequencies of key variants in metformin transporters within a Mexican population, addressing the interindividual variability in drug response. Genetic analysis was conducted on 101 healthy, unrelated Mexican subjects who were genotyped for the MATE1, MATE2, and OCT2 variants using allele-specific real-time PCR assays. The allele frequencies were 0.07 for OCT2, 0.23 for MATE1, and 0.67 for MATE2. The g.-66T→C variant was found only in wild-type and heterozygous forms. Comparative analysis indicated significant differences in allele frequencies between this Mexican population and other ethnic groups, highlighting potential implications for metformin efficacy and safety. This study provides crucial insights into the genetic variability of metformin transporter genes in a Mexican population, offering a foundation for personalized therapeutic approaches in type 2 diabetes management.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2024.1466394