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Population diversity of three variants of the SLC47A2 gene (MATE2-K transporter) in Mexican Mestizos and Native Americans

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Abstract

Background

MATE2-K is an efflux transporter protein of organic cation expressed mainly in the kidney and encoded by the SLC47A2 gene. Different variants of this gene have shown an impact on the pharmacokinetics of various drugs, including metformin, which represents one of the most widely used drugs in treating type 2 diabetes. The SLC47A2 gene variants have been scarcely studied in Mexican populations, especially in Native American groups. For this reason, we analyzed the distribution of the variants rs12943590, rs35263947, and rs9900497 within the SLC47A2 gene in 173 Native Americans (Tarahumara, Huichol, Maya, Puerépecha) and 182 Mestizos (admixed) individuals from Mexico.

Methods and results

Genotypes were determined through TaqMan probes (qPCR). The Hardy–Weinberg agreement was confirmed for all three SLC47A2 gene variants in all the Mexican populations analyzed. When worldwide populations were included for comparison purposes, for alleles and genotypes a relative interpopulation homogeneity was observed for rs35263947 (T allele; range 23.3–51.1%) and rs9900497 (T allele; range 18.6–40.9%). Conversely, heterogeneity was evident for rs12943590 (A allele, range 22.1–59.1%), where the most differentiated population was the Huichol, with high frequencies of the risk genotype associated with decreased response to metformin treatment (A/A = 40.9%).

Conclusions

Although the SLC47A2 gene variants allow predicting favorable response to the metformin treatment in Mexican populations, the probable high frequency of ineffectiveness should be discarded in Huichols.

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Acknowledgements

The authors wish to thank the volunteers who participate in this study and the PhD Elba Margarita Romero Tejeda for the technical support for the writing of the paper. We also thank the Universidad de Guadalajara (UdeG) for the economic support to this project to AFFM and HRV in the PROSNI 2019–2020 and infrastructure 2019 programs.

Funding

The grant from Infrastructure 2019 program of the University of Guadalajara (UdeG) to HR-V and AFF-M.

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Authors and Affiliations

  1. Instituto de Investigación en Genética Molecular, Centro Universitario de la Ciénega, Universidad de Guadalajara (CUCiénega-UdeG), Av. Universidad, No. 1115, Col. Lindavista, CP. 47810, Ocotlán, Jalisco, Mexico

    Alma Faviola Favela-Mendoza, Wendy Fernanda Cuevas-Sánchez, José Alonso Aguilar-Velázquez, Gabriela Martínez-Cortés & Héctor Rangel-Villalobos

  2. HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villega, Mexico City, Mexico

    Ingrid Fricke-Galindo

Authors
  1. Alma Faviola Favela-Mendoza
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  2. Ingrid Fricke-Galindo
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  3. Wendy Fernanda Cuevas-Sánchez
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  4. José Alonso Aguilar-Velázquez
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  5. Gabriela Martínez-Cortés
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  6. Héctor Rangel-Villalobos
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Contributions

The concept and design of the experiments were performed by F-MAF, R-VH. Performance of the experiments: C-SW, F-MAF. Data analysis: A-VJA, F-GI, F-MAF. Contributed reagents/materials/analysis tools: F-MAF, M-CG, R-VH. Wrote the paper: F-MAF, R-VH.

Corresponding authors

Correspondence to Alma Faviola Favela-Mendoza or Héctor Rangel-Villalobos.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All Mexican volunteers signed a written informed consent according to the ethical guidelines of the Helsinki Declaration. The Committee of Ethics and Research of the Centro Universitario de la Ciénega of the Universidad de Guadalajara (CUCI-UdeG, Mexico) approved this project. The anonymity of the recruited individuals was always preserved.

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Favela-Mendoza, A.F., Fricke-Galindo, I., Cuevas-Sánchez, W.F. et al. Population diversity of three variants of the SLC47A2 gene (MATE2-K transporter) in Mexican Mestizos and Native Americans. Mol Biol Rep 48, 6343–6348 (2021). https://doi.org/10.1007/s11033-021-06628-y

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