Cytochrome P450 single nucleotide polymorphisms in an indigenous Tanzanian population: a concern about the metabolism of artemisinin-based combinations

Malaria Journal

Research

Erasmus Kamugisha¹  Karol J Marwa²  Maria Sjögren³  Theresa Schmidt³  Göte Swedberg³  Omary MS Minzi⁴ 

[1] Department of Biochemistry, Catholic University of Health and Allied Sciences, Mwanza, Tanzania;Department of Pharmacology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania;Institute of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden;Unit of Pharmacology and Therapeutics, Muhimbili University of Health and Allied Health Sciences, Dar Es Salaam, Tanzania;

关键词: Cytochrome P450;    Artemisinin-based combination therapy;    Poor metabolizers;    Tanzania;    Plasmodium falciparum;   

DOI  :  10.1186/1475-2875-13-420

 received in 2014-08-23, accepted in 2014-10-25,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundArtemisinin-based combinations currently recommended for treatment of uncomplicated Plasmodium falciparum malaria in many countries of sub-Saharan Africa are substrates of CYP enzymes. The cytochrome enzyme system is responsible for metabolism of about 80-90% of clinically used drugs. It is, therefore, important to obtain the pharmacogenetics of the population in the region with respect to these combinations and thereby enable practitioners to predict treatment outcomes. The aim of this study was to detect and determine allelic frequencies of CYP2C8*2, CYP2C8*3, CYP3A4*1B, CYP3A5*3 and CYP2B6*6 variant alleles in a Tanzanian indigenous population.MethodsGenomic DNA extraction from blood obtained from 256 participants who escorted patients at Karume Health Centre in Mwanza Tanzania, was carried out using the Gene JET™ Genomic DNA purification kit (Thermo Scientific). Genotyping for the cytochrome P450 variant alleles was performed using predesigned primers. Amplification was done by PCR while differentiation between alleles was done by restriction fragment length polymorphism (PCR-RFLP) (for CYP2C8*2, CYP2C8*3) and sequencing (for CYP2B6*6, CYP3A5*3 and CYP3A4*1B).ResultsCYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A4*1B and CYP2B6*6 variant allelic frequencies were found to be 19,10,16,78 and 36% respectively.ConclusionPrevalence of CYP2C8*2, CYP3A5*3, CYP3A4*1B and CYP2B6*6 mutations in a Tanzanian population/subjects are common. The impact of these point mutations on the metabolism of anti-malarial drugs, particularly artemisinin-based combinations, and their potential drug-drug interactions (DDIs) needs to be further evaluated.

【 授权许可】

CC BY   
© Marwa et al.; licensee BioMed Central Ltd. 2014