title: Cytochrome P450 2C8*2 allele in Botswana: Human genetic diversity and public health implications.
abstract: Human cytochrome P450 2C8 is a highly polymorphic gene and shows variation according to ethnicity. The CYP2C8*2 is a slow drug metabolism allele and shows 10-24% frequency in Black populations. The objective of this study was to assess the prevalence of CYP2C8*2 allele in Botswana among the San (or Bushmen) and the Bantu ethnic groups. For that purpose we recruited 544 children of the two ethnicities in three districts of Botswana from primary schools, collected blood samples, extracted DNA and genotyped them through PCR-based restriction fragment length polymorphism analysis. The results demonstrated that in the San the prevalence of the CYP2C8*2 allele is significantly higher than among the Bantu-related ethnic groups (17.5% and 8.5% for San and Bantu, respectively; P=0.00002). These findings support the evidence of a different genetic background of the San with respect to Bantu-related populations, and highlight a possible higher risk of longer drug clearance or poor level of activation of pro-drugs among the San group.
authors.affiliation: Botswana Ministry of Health, Plot 54609, 24 Amos Street, Gaborone, Botswana; Medical Education Partnership Initiative (MEPI) Laboratory, Private Bag UB 00712, Gaborone, Botswana.
authors.forename: Thato
authors.initials: T
authors.lastname: Motshoge
authors.affiliation: Medical Education Partnership Initiative (MEPI) Laboratory, Private Bag UB 00712, Gaborone, Botswana; Botswana-University of Pennsylvania Partnership, P.O. Box AC 157 ACH, Gaborone, Botswana.
authors.forename: Leabaneng
authors.initials: L
authors.lastname: Tawe
authors.affiliation: Medical Education Partnership Initiative (MEPI) Laboratory, Private Bag UB 00712, Gaborone, Botswana; Botswana-University of Pennsylvania Partnership, P.O. Box AC 157 ACH, Gaborone, Botswana.
authors.forename: Charles Waithaka
authors.initials: CW
authors.lastname: Muthoga
authors.affiliation: Department of Oncology, University of Sheffield, Beech Hill Road, S10 2RX Sheffield, UK.
authors.forename: Joel
authors.initials: J
authors.lastname: Allotey
authors.affiliation: Department of Public Health and Infectious Diseases, University of Rome "La Sapienza", P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Romano
authors.affiliation: Department of Biochemistry, University of Namibia School of Medicine, Private Bag 13301, Windhoek, Namibia.
authors.forename: Isaac
authors.initials: I
authors.lastname: Quaye
authors.affiliation: Medical Education Partnership Initiative (MEPI) Laboratory, Private Bag UB 00712, Gaborone, Botswana; Botswana-University of Pennsylvania Partnership, P.O. Box AC 157 ACH, Gaborone, Botswana; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6073, USA. Electronic address: paganottig@botswana-upenn.co.bw.
authors.forename: Giacomo Maria
authors.initials: GM
authors.lastname: Paganotti
mesh_terms: D000293:Adolescent; D000483:Alleles; D044383:Black People / Q000235:genetics*; D001902:Botswana; D002648:Child; D065727:Cytochrome P-450 CYP2C8 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D003577:Cytochrome P-450 Enzyme System; D065727:Cytochrome P-450 CYP2C8
keywords: Bantu ethnic group; Botswana; CYP2C8; Pharmacogenetics; San ethnic group