title: Analysis of pharmacogenetic traits in two distinct South African populations.
abstract: Our knowledge of pharmacogenetic variability in diverse populations is scarce, especially in sub-Saharan Africa. To bridge this gap in knowledge, we characterised population frequencies of clinically relevant pharmacogenetic traits in two distinct South African population groups. We genotyped 211 tagging single nucleotide polymorphisms (tagSNPs) in 12 genes that influence antiretroviral drug disposition, in 176 South African individuals belonging to two distinct population groups residing in the Western Cape: the Xhosa (n = 109) and Cape Mixed Ancestry (CMA) (n = 67) groups. The minor allele frequencies (MAFs) of eight tagSNPs in six genes (those encoding the ATP binding cassette sub-family B, member 1 [ABCB1], four members of the cytochrome P450 family [CYP2A7P1, CYP2C18, CYP3A4, CYP3A5] and UDP-glucuronosyltransferase 1 [UGT1A1]) were significantly different between the Xhosa and CMA populations (Bonferroni p < 0.05). Twenty-seven haplotypes were inferred in four genes (CYP2C18, CYP3A4, the gene encoding solute carrier family 22 member 6 [SLC22A6] and UGT1A1) between the two South African populations. Characterising the Xhosa and CMA population frequencies of variant alleles important for drug transport and metabolism can help to establish the clinical relevance of pharmacogenetic testing in these populations.
authors.affiliation: University of California, San Francisco, School of Pharmacy, Department of Clinical Pharmacy, CA 94143, USA. ikediobio@pharmacy.ucsf.edu
authors.forename: Ogechi
authors.initials: O
authors.lastname: Ikediobi
authors.forename: Bradley
authors.initials: B
authors.lastname: Aouizerat
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Monica
authors.initials: M
authors.lastname: Gandhi
authors.forename: Stefan
authors.initials: S
authors.lastname: Gebhardt
authors.forename: Louise
authors.initials: L
authors.lastname: Warnich
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D054316:Biomarkers, Pharmacological; D044383:Black People / Q000235:genetics*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D014453:Glucuronosyltransferase / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011153:Population / Q000235:genetics*; D013019:South Africa; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001189:Aryl Hydrocarbon Hydroxylases; D054316:Biomarkers, Pharmacological; D050071:Bone Density Conservation Agents; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D000072467:Cytochrome P450 Family 2; D005819:Genetic Markers; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C513055:ABCB1 protein, human; C423964:CYP2A7 protein, human; C082185:CYP2C18 protein, human; C473667:cytochrome P-450 CYP3A45; C510163:CYP3A4 protein, human