title: Cytochrome P450 single nucleotide polymorphisms in an indigenous Tanzanian population: a concern about the metabolism of artemisinin-based combinations.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania. carol_maro@yahoo.com.
authors.forename: Karol J
authors.initials: KJ
authors.lastname: Marwa
authors.forename: Theresa
authors.initials: T
authors.lastname: Schmidt
authors.forename: Maria
authors.initials: M
authors.lastname: Sjögren
authors.forename: Omary M S
authors.initials: OM
authors.lastname: Minzi
authors.forename: Erasmus
authors.initials: E
authors.lastname: Kamugisha
authors.forename: Göte
authors.initials: G
authors.lastname: Swedberg
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics* / Q000627:therapeutic use; D037621:Artemisinins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013636:Tanzania / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D003577:Cytochrome P-450 Enzyme System; C031327:artemisinin