Genetic variants in CYP (-1A2,-2C9,-2C19,-3A4 and-3A5), VKORC1 and ABCB1 genes in a black South African population: a window into diversity

Aim: The frequencies of variants of pharmacogenetic importance differ across populations. African populations exhibit the greatest genetic heterogeneity, cautioning against extrapolating results among African groups. The aim of this study was to genotype pharmacogenetically relevant variants in black South Africans, to expand the limited data set available for indigenous African populations. Subjects & methods: A total of 14 SNPs associated with seven genes known to influence drug metabolism or transport (CYP1A2, CYP2C19, CYP2C9, CYP3A4, CYP3A5, VKORC1 and ABCB1) were investigated in a South African black (SAB) population (n = 993) and allele frequencies were compared with populations of African, Asian and European origin. Results: The majority of SNPs in the SAB demonstrated significant allele frequency differences when compared with both Europeans and Asians. There was greater similarity between the SAB and the Luhya (Kenya) and the Yoruba (Nigeria), than with Maasai (Kenya) individuals. The CYP2C9 SNP (rs1799853) was not polymorphic in the SAB and two VKORC1 SNPs (rs17708472 and rs9934438) had low variant allele frequencies, limiting their relevance to warfarin dose in this population. Population differences are emphasized by the significant differences in ABCB1 and the CYP3A gene family allele frequencies, with implications for drug metabolism and transport. Conclusion: This study highlights the importance of investigating and documenting genetic variation at loci of pharmacogenetic relevance among different populations since this information could be used to inform drug efficacy, safety and recommended dosage.