抄録
Background: Warfarin is the most commonly used anticoagulant and exhibits a huge variability in the starting doses required to achieve the international normalised ratio (INR). Many genetic-association studies (GWAS) have reported on European and Asian populations which has led to the designing of specific algorithms that are now being used and presented as universally applicable in assisting decision making in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR exist. In this study, we set out to investigate SNPs in genes affecting the disposition of warfarin therapy.
Methods: A total of 260 participants were recruited from Cape Town, South Africa (n=160) and Harare, Zimbabwe (n=100). DNA was extracted from blood and subsequently genotyped using PCR/RFLP, Sanger sequencing and iPlex Mass arrays for the 74 SNPs and CNVs in 20 genes, going beyond the traditional three genes, VKORC1, CYP2C9 and CYP4F2.
Results: Several observations were made among which include new associations of certain variants with warfarin response. We report associations of warfarin dose with age, BMI and selective effects of SNPs giving unique profile of genetic variants that are associated with warfarin pharmacogenetics among Africans.
Conclusion: We conclude African participants present with a unique set of genetic variants that affects responses to warfarin therapy. It is our hope that this knowledge in warfarin pharmacogenomics could help in the judicious use of this drug as well as planning of pharmacogenetics tests to be used alongside warfarin therapy.
