Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis

Innocent G. Asiimwe*, Eunice J. Zhang, Rostam Osanlou, Amanda Krause, Chrisly Dillon, Guilherme Suarez-Kurtz, Honghong Zhang, Jamila A. Perini, Jessicca Y. Renta, Jorge Duconge, Larisa H. Cavallari, Leiliane R. Marcatto, Mark T. Beasly, Minoli A. Perera, Nita A. Limdi, Paulo C.J.L. Santos, Stephen E. Kimmel, Steven A. Lubitz, Stuart A. Scott, Vivian K. KawaiAndrea L. Jorgensen, Munir Pirmohamed

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively. VKORC1 variants rs9923231 (-1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2C gene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black-Africans to evaluate genetic factors determining warfarin response.

Original languageEnglish (US)
Pages (from-to)1420-1433
Number of pages14
JournalClinical pharmacology and therapeutics
Volume107
Issue number6
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Asiimwe, I. G., Zhang, E. J., Osanlou, R., Krause, A., Dillon, C., Suarez-Kurtz, G., Zhang, H., Perini, J. A., Renta, J. Y., Duconge, J., Cavallari, L. H., Marcatto, L. R., Beasly, M. T., Perera, M. A., Limdi, N. A., Santos, P. C. J. L., Kimmel, S. E., Lubitz, S. A., Scott, S. A., ... Pirmohamed, M. (2020). Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis. Clinical pharmacology and therapeutics, 107(6), 1420-1433. https://doi.org/10.1002/cpt.1755