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

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 (C allele; range: 48.9–76.7%) and rs9900497 (G allele; range: 59.1–81.4%). Conversely, heterogeneity was evident for rs12943590 (G allele, range 40.9–77.9%), 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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Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics)

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2015-0030 ◽

2016 ◽

Vol 31 (2) ◽

Cited By ~ 4

Author(s):

Ingrid Fricke-Galindo ◽

Helgi Jung-Cook ◽

Adrián LLerena ◽

Marisol López-López

Keyword(s):

Healthy Volunteers ◽

Literature Search ◽

Population Diversity ◽

Allele Frequencies ◽

Inclusion Criteria ◽

Metabolic Phenotypes ◽

Complex Population ◽

Mexican Mestizos ◽

Mexican Populations

AbstractMexico presents a complex population diversity integrated by Mexican indigenous (MI) (7% of Mexico’s population) and Mexican mestizos (MMs). This composition highlights the importance of pharmacogenetic studies in Mexican populations. The aims of this study were to analyze the reported frequencies of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in healthy volunteers from Mexican populations and to assess its interethnic variability across MI and MM populations. After a literature search in PubMed, and according to previously defined inclusion criteria, 63 pharmacogenetic studies performed in Mexican healthy volunteers up to date were selected. These reports comprised 56,292 healthy volunteers (71.58% MM). Allele frequencies in 31 pharmacogenetic biomarkers, from 121 searched, are described. Nine of these biomarkers presented variation within MM and MI groups. The frequencies of

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