Abstract
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. 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%). 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.
Highlights
Multidrug and toxin extrusion proteins (MATE), named MATE1 and MATE2, mediate organic cations' efflux through the luminal membrane on renal proximal tubule cells and canalicular membrane of hepatocytes
It is worth mention that metformin is used as a first-line treatment in patients with type 2 diabetes mellitus (T2DM), and its therapeutic response is apparently affected by the presence of triplotypes composed by the interaction of rs72552763, rs622342 for OCT1, and rs12943590 for SLC47A2 [2,9,13]
The genotype distribution agreed with Hardy-Weinberg's expectations for all three SLC47A2 gene variants in the eight Mexican populations (Table 1)
Summary
Multidrug and toxin extrusion proteins (MATE), named MATE1 and MATE2, mediate organic cations' efflux through the luminal membrane on renal proximal tubule cells and canalicular membrane of hepatocytes. 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. 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%). 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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