In:
Clinical Pharmacology & Therapeutics, Wiley, Vol. 107, No. 6 ( 2020-06), p. 1420-1433
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.
Type of Medium:
Online Resource
ISSN:
0009-9236
,
1532-6535
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2040184-X
SSG:
15,3
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