Abstract

Membrane transporters play a critical role in drug response as they provide the targets for many commonly used drugs and are major determinants of drug absorption, distribution, and elimination. Most of them belong to one of the two major super-families of membrane transport proteins, the ATP-binding cassette (ABC) transporters, and the solute carrier (SLC) transporters. They are subject to both genotypic and phenotypic polymorphisms, and variation in drug transporters may be the reason for inter-individual variability in pharmacokinetic disposition, efficacy, and toxicity of drug transporter substrates. The growing number of publications reporting genetic population data for the solute carrier transporters in particular shows their importance, as well as the increased interest in investigating them in most recent pharmaco-genetics/genomics research projects. These publications range from reporting baseline frequency distributions of SNPs of genes important in drug transport, discovering new genetic variants of these genes, and/or describing genotyping projects to identify probable responders or non-responders to therapy, or to predict exposure levels in different patients. This paper reviews the solute carrier transporters and highlights the fact that there is much to be learnt from characterizing human genomic variation in South Africa and sub-Saharan Africa, especially with regards to health applications. Genomic diversity in this region is indeed relatively under-studied despite being home to significant portion of human genomic diversity.

Key words: Solute carrier transporters, pharmacogenomics, pharmacogenetics.

Abbreviation

Abbreviations: ABC, ATP-binding cassette; SNPs, single nucleotide polymorphisms; VNTR, variable number of tandem repeat polymorphisms; PGx,pharmacogenomics; PGt, pharmacogenetics; MDR, multidrug resistance; SLC,solute carrier; OCTs, organic cation transporters; OATs, organic anion transporters; OCTNs, organic zwitterion/cation transporters; MATE, multidrug and toxin extrusion.