2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Genetic Diversity in Drug Transporters: Impact in African Populations

      review-article
      1 , , 2 , 3
      Clinical and Translational Science
      John Wiley and Sons Inc.

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Polymorphisms in drug transporters, like the adenosine triposphate‒binding cassette (ABC) and solute carrier (SLC) superfamilies, may contribute to the observed diversity in drug response in African patients. This review aims to provide a comprehensive summary and analysis of the frequencies and distributions in African populations of ABC and SLC variants that affect drug pharmacokinetics (PK) and pharmacodynamics (PD). Of polymorphisms evaluated in African populations, SLCO1B1 rs4149056 and SLC22A6 rs1158626 were found at markedly higher frequencies than in non‐African populations. SLCO1B1 rs4149056 was associated with reduction in rifampin exposure, which has implications for dosing this important anti‐tuberculosis therapy. SLC22A6 rs1158626 was associated with increased affinity for antiretroviral drugs. Genetic diversity in SLC and ABC transporters in African populations has implications for conventional therapies, notably in tuberculosis and HIV. More PK and PD data in African populations are needed to assess potential for a different response to drugs compared with other global populations.

          Related collections

          Most cited references57

          • Record: found
          • Abstract: found
          • Article: not found

          The genetic structure and history of Africans and African Americans.

          Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Human ATP-binding cassette (ABC) transporter family

            There exist four fundamentally different classes of membrane-bound transport proteins: ion channels; transporters; aquaporins; and ATP-powered pumps. ATP-binding cassette (ABC) transporters are an example of ATP-dependent pumps. ABC transporters are ubiquitous membrane-bound proteins, present in all prokaryotes, as well as plants, fungi, yeast and animals. These pumps can move substrates in (influx) or out (efflux) of cells. In mammals, ABC transporters are expressed predominantly in the liver, intestine, blood-brain barrier, blood-testis barrier, placenta and kidney. ABC proteins transport a number of endogenous substrates, including inorganic anions, metal ions, peptides, amino acids, sugars and a large number of hydrophobic compounds and metabolites across the plasma membrane, and also across intracellular membranes. The human genome contains 49 ABC genes, arranged in eight subfamilies and named via divergent evolution. That ABC genes are important is underscored by the fact that mutations in at least I I of these genes are already known to cause severe inherited diseases (eg cystic fibrosis and X-linked adrenoleukodystrophy [X-ALD]). ABC transporters also participate in the movement of most drugs and their metabolites across cell surface and cellular organelle membranes; thus, defects in these genes can be important in terms of cancer therapy, pharmacokinetics and innumerable pharmacogenetic disorders.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Physicochemical properties of antibacterial compounds: implications for drug discovery.

                Bookmark

                Author and article information

                Contributors
                iris.rajman@novartis.com
                Journal
                Clin Transl Sci
                Clin Transl Sci
                10.1111/(ISSN)1752-8062
                CTS
                Clinical and Translational Science
                John Wiley and Sons Inc. (Hoboken )
                1752-8054
                1752-8062
                31 March 2020
                September 2020
                : 13
                : 5 ( doiID: 10.1111/cts.v13.5 )
                : 848-860
                Affiliations
                [ 1 ] Novartis NKK Tokyo Japan
                [ 2 ] PharmaGenesis London London UK
                [ 3 ] Novartis East Hanover New Jersey USA
                Author notes
                [*] [* ] Correspondence: Iris Rajman ( iris.rajman@ 123456novartis.com )

                Article
                CTS12769
                10.1111/cts.12769
                7485953
                32100958
                046fdbb3-7af4-435b-9fb9-a97117b38a93
                © 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society of Clinical Pharmacology and Therapeutics.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 10 December 2019
                : 04 January 2020
                Page count
                Figures: 1, Tables: 6, Pages: 13, Words: 10619
                Funding
                Funded by: Novartis Pharma AG
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                September 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.0 mode:remove_FC converted:11.09.2020

                Medicine
                Medicine

                Comments

                Comment on this article