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种族多样性与华法林药物基因组学

Ethnic Diversity and Warfarin Pharmacogenomics.

作者信息

Asiimwe Innocent G, Pirmohamed Munir

机构信息

The Wolfson Centre for Personalized Medicine, MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

出版信息

Front Pharmacol. 2022 Apr 4;13:866058. doi: 10.3389/fphar.2022.866058. eCollection 2022.

Abstract

Warfarin has remained the most commonly prescribed vitamin K oral anticoagulant worldwide since its approval in 1954. Dosing challenges including having a narrow therapeutic window and a wide interpatient variability in dosing requirements have contributed to making it the most studied drug in terms of genotype-phenotype relationships. However, most of these studies have been conducted in Whites or Asians which means the current pharmacogenomics evidence-base does not reflect ethnic diversity. Due to differences in minor allele frequencies of key genetic variants, studies conducted in Whites/Asians may not be applicable to underrepresented populations such as Blacks, Hispanics/Latinos, American Indians/Alaska Natives and Native Hawaiians/other Pacific Islanders. This may exacerbate health inequalities when Whites/Asians have better anticoagulation profiles due to the existence of validated pharmacogenomic dosing algorithms which fail to perform similarly in the underrepresented populations. To examine the extent to which individual races/ethnicities are represented in the existing body of pharmacogenomic evidence, we review evidence pertaining to published pharmacogenomic dosing algorithms, including clinical utility studies, cost-effectiveness studies and clinical implementation guidelines that have been published in the warfarin field.

摘要

自1954年获批以来,华法林一直是全球最常用的维生素K口服抗凝剂。给药方面的挑战,包括治疗窗狭窄和患者间给药需求差异大,使得它成为基因-表型关系研究最多的药物。然而,这些研究大多在白种人或亚洲人中进行,这意味着目前的药物基因组学证据基础并未反映种族多样性。由于关键基因变异的次要等位基因频率存在差异,在白种人/亚洲人中进行的研究可能不适用于黑人、西班牙裔/拉丁裔、美洲印第安人/阿拉斯加原住民以及夏威夷原住民/其他太平洋岛民等代表性不足的人群。当白种人/亚洲人因存在经过验证的药物基因组学给药算法而具有更好的抗凝效果,而这些算法在代表性不足的人群中表现不佳时,这可能会加剧健康不平等。为了研究现有药物基因组学证据中各个种族/族裔的代表性程度,我们回顾了与已发表的药物基因组学给药算法相关的证据,包括华法林领域已发表的临床效用研究、成本效益研究和临床实施指南。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aefa/9014219/e318800e0988/fphar-13-866058-g001.jpg

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