Genetic Diversity in Drug Transporters: Impact in African Populations

被引:11
|
作者
Rajman, Iris [1 ]
Knapp, Laura [2 ]
Hanna, Imad [3 ]
机构
[1] Novartis NKK, Tokyo, Japan
[2] PharmaGenesis London, London, England
[3] Novartis, E Hanover, NJ USA
来源
关键词
SINGLE NUCLEOTIDE POLYMORPHISMS; NEVIRAPINE PLASMA-CONCENTRATIONS; HIV-INFECTED PATIENTS; PHYSICOCHEMICAL PROPERTIES; RIFAMPICIN CONCENTRATIONS; SLCO1B1; POLYMORPHISMS; PRECISION MEDICINE; SCHOOL-CHILDREN; RISK-FACTORS; RIVER-BASIN;
D O I
10.1111/cts.12769
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:848 / 860
页数:13
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