Genetic factors influencing warfarin dose in Black-African patients: a systematic review and meta-analysis.



Asiimwe, Innocent G ORCID: 0000-0002-1196-1822, Zhang, Eunice J, Osanlou, Rostam, Krause, Amanda, Dillon, Chrisly, Suarez-Kurtz, Guilherme, Zhang, Honghong, Perini, Jamila A, Renta, Jessicca Y, Duconge, Jorge
et al (show 12 more authors) (2020) Genetic factors influencing warfarin dose in Black-African patients: a systematic review and meta-analysis. Clinical Pharmacology and Therapeutics, 107 (6). 1420 - 1433.

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Abstract

Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high inter-individual 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 while 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.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 03 Jan 2020 12:09
Last Modified: 05 May 2021 12:02
DOI: 10.1002/cpt.1755
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3067863