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Observational Study
. 2023 Jul;24(10):529-538.
doi: 10.2217/pgs-2023-0089. Epub 2023 Jul 12.

Warfarin pharmacogenetics in a black Zimbabwean cohort: an observational prospective study

Marie Madeleine M Hidjo  1   2 , Zedias Chikwambi  1   2 , Gift Ngwende  3 , Jonathan A Matenga  3 , Collen Masimirembwa  1
Affiliations
Observational Study

Warfarin pharmacogenetics in a black Zimbabwean cohort: an observational prospective study

Marie Madeleine M Hidjo et al. Pharmacogenomics. 2023 Jul.

Abstract

Aim: A prospective observational study was conducted to evaluate the feasibility of implementing clinical guidelines for warfarin dosing in black Zimbabwean patients. Methods: CYP2C9*5, CYP2C9*6, CYP2C9*8 and CYP2C9*11 and VKORC1 c. 1639 G>A variations were observed in 62 study patients. Results & Conclusion: Overall, 39/62 (62.90%) participants did not receive a warfarin starting dose as would have been recommended by Clinical Pharmacogenetics Implementation Consortium guidelines. US FDA and Dutch Pharmacogenetics Working Group guidelines are based on CYP2C9*2 and CYP2C9*3 only, hence, unlikely useful in this cohort, where such variants were not detected. Clinical Pharmacogenetics Implementation Consortium guidelines, on the other hand, have a specific recommendation on the African-specific variants CYP2C9*5, CYP2C9*6 and CYP2C9*11, and are hence suitable for implementation in Zimbabwe and would help optimize warfarin doses in patients in the study cohort.

Keywords: CYP2C9; VKORC1; genetic variation; pharmacogenomics; warfarin.

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Conflict of interest statement

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.. CYP2C9 and VKORC1 1639 G>A genotype frequencies.
AA and GG are homozygous, AG is heterozygous.
Figure 2.
Figure 2.. Warfarin starting dose considering CYP2C9, VKORC1 and FDA, Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group guidelines.
AA and GG are homozygous, AG is heterozygous.
Figure 3.
Figure 3.. International normalized ratio predictive of recommended warfarin starting dose considering FDA, Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group guidelines.
INR: International normalized ratio.
Figure 4.
Figure 4.. International normalized ratio and participant monitoring.
INR: International normalized ratio.
Figure 5.
Figure 5.. International normalized ratio distribution based on CYP2C9 genotype.
IM: Intermediate metaboliser; INR: International normalized ratio; NM: Normal metaboliser; PM: Poor metaboliser.
Figure 6.
Figure 6.. Participant distribution across CYP2C9 and VKORC1 1639 G>A genotypes based on warfarin starting dose.
See this image and copyright information in PMC

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