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The population attributable fraction as a measure of the impact of warfarin pharmacogenetic testing

机译:人口归因分数,用于衡量华法林药物遗传学检测的影响

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Aim: We aimed to estimate the population impact of warfarin pharmacogenetic testing (WPGT) across multiple populations. Materials & methods: We used the expanded International Warfarin Pharmacogenetics Consortium data set and genotype frequencies from HapMap to simulate dose distributions for each CYP2C9/VKORC1 genotype combination in the different races, and calculated the population attributable fraction as a measure of population impact of WPGT. WPGT was compared to both clinical and fixed-dose algorithms to estimate the benefits of WPGT. Results: Our dose simulation revealed different dose requirements in difference races and considerable overlap in dose distributions of different genotype combinations. Population attributable fraction calculations suggest that complete implementation of WPGT can reduce inaccurate dosing by 18-24% in white individuals. However black, Japanese and Chinese patients do not benefit from WPGT, especially when compared against a race-specific fixed dose. Conclusion: Our findings support WPGT in white individuals but not in black, Japanese and Chinese individuals. Original submitted 28 March 2012; Revision submitted 11 June 201.
机译:目的:我们旨在评估华法林药物遗传测试(WPGT)对多个人群的影响。材料和方法:我们使用来自HapMap的扩展的国际华法林药物遗传学联合会数据集和基因型频率来模拟不同种族中每种CYP2C9 / VKORC1基因型组合的剂量分布,并计算人口归因分数作为衡量WPGT对人口影响的量度。将WPGT与临床和固定剂量算法进行比较,以评估WPGT的益处。结果:我们的剂量模拟显示不同种族的剂量要求不同,并且不同基因型组合的剂量分布有相当大的重叠。人群可归因分数计算表明,完全实施WPGT可以使白人个体的不准确剂量减少18-24%。但是,黑人,日本人和中国人并未从WPGT中受益,特别是与种族专用的固定剂量相比时。结论:我们的发现支持白人个体的WPGT,但不支持黑人,日本和中国个体。原件于2012年3月28日提交;修订于201年6月11日提交。

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