Genetic Preservation of SLC22A3 in Local South African Populations

Abstract

Abstract Organic cation transporters of the amphiphilic solute facilitator family of membrane proteins are involved in the translocation of a diverse range of endogenous and exogenous organic cations. These organic cations include clinically important substrates such as the anti-diabetic drug metformin, the anti-neoplastic drug oxaliplatin, and the anti-retroviral drug lamivudine. Inter-individual variation in drug disposition and efficacy is a major clinical problem and the role of these transporters is increasingly being recognized as a possible mechanism explaining this variation. Moreover, it is estimated that between 15 and 30% of interindividual variation in drug disposition and response is a result of genetic factors The aim of this study was to determine the baseline minor allele frequency distribution of 18 known coding SNPs in the SLC22A3 gene of ~ 140 Cape Admixed and Xhosa individuals residing in Cape Town, South Africa. This study found no genetic polymorphisms in the coding region of the SLC22A3 gene of the Xhosa individuals investigated. This study has shown that SLC22A3 coding SNPs observed in other populations are absent in the sample of both Cape Admixed and Xhosa individuals studied. The lack of protein sequence variation was consistent with other studies and may reflect the significant physiological role of hOCT3 in maintaining cellular and organismal homeostasis.