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

Nyarai Desiree Soko; Emile Chimusa; Collen Masimirembwa; Collet Dandara

doi:10.1038/s41397-018-0035-3

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. 2019 Jun;19(3):240-248. doi: 10.1038/s41397-018-0035-3. Epub 2018 Aug 13.

Authors

Nyarai Desiree Soko¹, Emile Chimusa¹, Collen Masimirembwa², Collet Dandara³

Affiliations

¹ Division of Human Genetic, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
² African Institute of Biomedical Science and Technology (AiBST), Wilkins Hospital, Corner Rekai Tangwena and Josiah Tongogara Ave, Harare, Zimbabwe.
³ Division of Human Genetic, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. collet.dandara@uct.ac.za.

PMID: 30100615
DOI: 10.1038/s41397-018-0035-3

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics*
Asian People / genetics
Black People / genetics
Exome / genetics
Genotype
Humans
Liver-Specific Organic Anion Transporter 1 / genetics*
Multidrug Resistance-Associated Protein 2
Neoplasm Proteins / genetics*
Pharmacogenetics / methods
Polymorphism, Single Nucleotide / genetics*
Rosuvastatin Calcium / blood*
Rosuvastatin Calcium / pharmacokinetics*
White People / genetics
Zimbabwe

Substances

ABCC2 protein, human
ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily G, Member 2
Liver-Specific Organic Anion Transporter 1
Multidrug Resistance-Associated Protein 2
Neoplasm Proteins
SLCO1B1 protein, human
Rosuvastatin Calcium