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An African-specific profile of pharmacogene variants for rosuvastatin plasma variability: limited role for SLCO1B1 c.521T>C and ABCG2 c.421A>C

The Pharmacogenomics Journal volume 19, pages 240–248 (2019)Cite this article

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Abstract

Studies in Caucasian and Asian populations consistently associated interindividual and interethnic variability in rosuvastatin pharmacokinetics to the polymorphisms SLCO1B1 c.521T>C (rs4149056 p. Val174Ala) and ABCG2 c.421C>A (rs2231142, p. Gln141Lys). To investigate the pharmacogenetics of rosuvastatin in African populations, we first screened 785 individuals from nine ethnic African populations for the SLCO1B1 c.521C and ABCG2 c.421CA variants. This was followed by sequencing whole exomes from individuals of African Bantu descent, who participated in a 20 mg rosuvastatin pharmacokinetic trial in Harare Zimbabwe. Frequencies of SLCO1B1 c.521C ranged from 0.0% (San) to 7.0% (Maasai), while ABCG2 c.421A ranged from 0.0% (Shona) to 5.0% (Kikuyu). Variants showing significant association with rosuvastatin exposure were identified in SLCO1B1, ABCC2, SLC10A2, ABCB11, AHR, HNF4A, RXRA and FOXA3, and appear to be African specific. Interindividual differences in the pharmacokinetics of rosuvastatin in this African cohort cannot be explained by the polymorphisms SLCO1B1 c.521T>C and ABCG2 c.421C>A, but appear driven by a different set of variants.

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Acknowledgements

We would like to acknowledge the University of Cape Town and Medical Research Council of South Africa for funding this research.

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Authors and Affiliations

  1. Division of Human Genetic, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

    Nyarai Desiree Soko, Emile Chimusa & Collet Dandara

  2. African Institute of Biomedical Science and Technology (AiBST), Wilkins Hospital, Corner Rekai Tangwena and Josiah Tongogara Ave, Harare, Zimbabwe

    Collen Masimirembwa

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Soko, N.D., Chimusa, E., Masimirembwa, C. et al. An African-specific profile of pharmacogene variants for rosuvastatin plasma variability: limited role for SLCO1B1 c.521T>C and ABCG2 c.421A>C. Pharmacogenomics J 19, 240–248 (2019). https://doi.org/10.1038/s41397-018-0035-3

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