| Literature DB >> 31869433 |
Innocent G Asiimwe1, Eunice J Zhang1, Rostam Osanlou1, Amanda Krause2, Chrisly Dillon3, Guilherme Suarez-Kurtz4, Honghong Zhang5, Jamila A Perini6, Jessicca Y Renta7, Jorge Duconge7, Larisa H Cavallari8, Leiliane R Marcatto9, Mark T Beasly3, Minoli A Perera5, Nita A Limdi3, Paulo C J L Santos10, Stephen E Kimmel11, Steven A Lubitz12, Stuart A Scott13,14, Vivian K Kawai15, Andrea L Jorgensen16, Munir Pirmohamed1.
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.Entities:
Mesh：
Substances：
Year: 2020 PMID： 31869433 PMCID： PMC7217737 DOI： 10.1002/cpt.1755
Source DB: PubMed Journal: Clin Pharmacol Ther ISSN： 0009-9236 Impact factor: 6.875