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

• Published in: Malaria journal 2014-11, Vol.13 (1), p.420-420, Article 420
• Main Authors: Marwa, Karol J, Schmidt, Theresa, Sjögren, Maria, Minzi, Omary M S, Kamugisha, Erasmus, Swedberg, Göte
• Format: Article
• Language: English
• Subjects: Adult; Antimalarials - pharmacokinetics; Antimalarials - therapeutic use; Artemisinin-based combination therapy; Artemisinins - pharmacokinetics; Artemisinins - therapeutic use; Care and treatment; Cross-Sectional Studies; Cytochrome P-450; Cytochrome P-450 Enzyme System - genetics; Cytochrome P450; Data analysis; Deoxyribonucleic acid; DNA; Drugs; Enzymes; Female; Gene Frequency; Genes; Genetic aspects; Humans; Malaria; Malaria - drug therapy; Malaria - epidemiology; Malaria - genetics; Male; Metabolism; Mutation; Physiological aspects; Plasmodium falciparum; Plasmodium falciparum malaria; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide - genetics; Poor metabolizers; Population; Prognosis; Single nucleotide polymorphisms; Studies; Tanzania; Tanzania - epidemiology; Young Adult
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/1475-2875-13-420

Artemisinin-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. Genomic 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). CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A4*1B and CYP2B6*6 variant allelic frequencies were found to be 19,10,16,78 and 36% respectively. Prevalence 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.