Division of Human Genetic, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
African Institute of Biomedical Science and Technology (AiBST), Wilkins Hospital, Corner Rekai Tangwena and Josiah Tongogara Ave, Harare, Zimbabwe.
Pharmacogenomics J. 2019 Jun;19(3):240-248. doi: 10.1038/s41397-018-0035-3. Epub 2018 Aug 13.
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.
在白种人和亚洲人群中的研究一致表明，洛伐他汀药代动力学的个体间和种族间变异性与 SLCO1B1 c.521T>C（rs4149056 p.Val174Ala）和 ABCG2 c.421C>A（rs2231142，p.Gln141Lys）多态性有关。为了研究洛伐他汀在非洲人群中的药物遗传学，我们首先在来自九个非洲种族群体的 785 个人中筛选了 SLCO1B1 c.521C 和 ABCG2 c.421CA 变体。随后，对来自非洲班图人的个体进行了全外显子测序，他们参加了在津巴布韦哈拉雷进行的 20mg 洛伐他汀药代动力学试验。SLCO1B1 c.521C 的频率范围从 0.0%（桑人）到 7.0%（马赛人），而 ABCG2 c.421A 的频率范围从 0.0%（绍纳人）到 5.0%（基库尤人）。在 SLCO1B1、ABCC2、SLC10A2、ABCB11、AHR、HNF4A、RXRA 和 FOXA3 中发现了与洛伐他汀暴露显著相关的变体，这些变体似乎是非洲特有的。在这个非洲队列中，洛伐他汀药代动力学的个体间差异不能用 SLCO1B1 c.521T>C 和 ABCG2 c.421C>A 多态性来解释，但似乎是由一组不同的变体驱动的。
