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.

中文翻译：

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影响非洲黑人患者华法林剂量的遗传因素：系统评价和荟萃分析。


华法林是撒哈拉以南非洲地区最常用的口服抗凝剂。由于治疗指数狭窄和剂量需求的个体间差异较大，给药具有挑战性。为了评估影响非洲黑人华法林剂量的遗传因素，我们对 48 项研究（2,336 名患者）进行了荟萃分析。 CYP2C9 和稳定剂量的显着预测因子包括 rs1799853 (CYP2C9*2)、rs1057910 (CYP2C9*3)、rs28371686 (CYP2C9*5)、rs9332131 (CYP2C9*6) 和 rs28371685 (CYP2C9*11)，使剂量减少 6.8， 12.5,分别为 13.4、8.1 和 5.3 毫克/周。 VKORC1 变体 rs9923231 (-1639G>A)、rs9934438 (1173C>T)、rs2359612 (2255C>T)、rs8050894 (1542G>C) 和 rs2884737 (497T>G) 使剂量减少 18.1、21.6、17.3、1 1.7，和分别为 19.6 毫克/周，而 rs7294 (3730G>A) 则将剂量增加了 6.9 毫克/周。最后，rs12777823（CYP2C 基因簇）与每周 12.7 毫克的剂量减少相关。在非洲进行的研究很少，而且患者数量也很少，这突出表明需要在非洲黑人中开展进一步的工作，以评估决定华法林反应的遗传因素。