Cytochrome P450 pharmacogenetics in African populations: implications for public health

被引:41
作者
Dandara, Collet [1 ]
Swart, Marelize [1 ]
Mpeta, Bafokeng [1 ]
Wonkam, Ambroise [2 ]
Masimirembwa, Collen [3 ]
机构
[1] Univ Cape Town, Pharmacogenet & Canc Res Grp, Dept Clin Lab Sci, Fac Hlth Sci,Div Human Genet, ZA-7925 Cape Town, South Africa
[2] Univ Cape Town, Fac Hlth Sci, Div Human Genet, Dept Clin Lab Sci, ZA-7925 Cape Town, South Africa
[3] African Inst Biomed Sci & Technol, Mol Sci Unit, Harare, Zimbabwe
基金
新加坡国家研究基金会; 英国医学研究理事会;
关键词
Africa; cytochrome P450; genetic diversity; genetics variation; pharmacogenetics; pharmacogenomics; public health; SINGLE NUCLEOTIDE POLYMORPHISMS; PLASMA EFAVIRENZ LEVELS; CYP2D6 MUTANT ALLELES; GENETIC POLYMORPHISMS; GENOTYPE FREQUENCIES; SPEAKING POPULATIONS; DECREASED CAPACITY; ETHNIC-DIFFERENCES; PREDICTIVE-VALUE; BLACK;
D O I
10.1517/17425255.2014.894020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Introduction: Africa harbors a disproportionate burden of disease when taking into account the triple challenge caused by HIV/AIDS, tuberculosis (TB) and malaria, against a backdrop of an increasing burden of noncommunicable diseases. More than 80% of therapeutic drugs used in the management of these diseases/conditions are metabolized by CYP enzymes that exhibit genetic polymorphisms. Areas covered: There is variability in the expression and activities of CYPs resulting in interindividual differences in the response to standard doses of therapeutic drugs, due to genetic polymorphisms, which exhibit both quantitative and qualitative differences between racial and between ethnic groups. The review aims to evaluate the implications of the genetic variation in CYPs on the public health of Africans. The CYPs reviewed here metabolize most of the commonly used therapeutic drugs and include CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 and 3A5. Allele frequencies are compared between African ethnic groups and among populations of African, Asian and European origin. Data are obtained from our own studies and literature. Expert opinion: The variability in the pattern of genetic variation between populations translates into differences in drug response. Understanding CYP variability improves rational drug use and has public health significance.
引用
收藏
页码:769 / 785
页数:17
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