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Genetic Factors Influencing Warfarin Dose in Black‐African Patients: A Systematic Review and Meta‐Analysis
Author(s) -
Asiimwe Innocent G.,
Zhang Eunice J.,
Osanlou Rostam,
Krause Amanda,
Dillon Chrisly,
SuarezKurtz Guilherme,
Zhang Honghong,
Perini Jamila A.,
Renta Jessicca Y.,
Duconge Jorge,
Cavallari Larisa H.,
Marcatto Leiliane R.,
Beasly Mark T.,
Perera Minoli A.,
Limdi Nita A.,
Santos Paulo C.J.L.,
Kimmel Stephen E.,
Lubitz Steven A.,
Scott Stuart A.,
Kawai Vivian K.,
Jorgensen Andrea L.,
Pirmohamed Munir
Publication year - 2020
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1755
Subject(s) - cyp2c9 , vkorc1 , warfarin , dosing , medicine , therapeutic index , maintenance dose , pharmacology , drug , atrial fibrillation , cytochrome p450 , metabolism
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.