Department of Pharmacy Practice and Science, University of Arizona College of Pharmacy, Tucson, Arizona.
Department of Pharmacology and Toxicology, University of Arizona College of Pharmacy, Tucson, Arizona.
Pharmacotherapy. 2017 Sep;37(9):1150-1163. doi: 10.1002/phar.1982. Epub 2017 Sep 6.
Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarin-related adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry. Despite differing frequencies of variants by race/ethnicity, most evidence in diverse populations evaluates variants that are most common in populations of European ancestry. Algorithms that do not include variants important across race/ethnic groups are unlikely to benefit diverse populations. In some race/ethnic groups, development of race-specific or admixture-based algorithms may facilitate improved genotype-guided warfarin dosing algorithms above and beyond that seen in individuals of European ancestry. These observations should be considered in the interpretation of literature evaluating the clinical utility of genotype-guided warfarin dosing. Careful consideration of race/ethnicity and additional evidence focused on improving warfarin dosing algorithms across race/ethnic groups will be necessary for successful clinical implementation of warfarin pharmacogenomics. The evidence for warfarin pharmacogenomics has a broad significance for pharmacogenomic testing, emphasizing the consideration of race/ethnicity in discovery of gene-drug pairs and development of clinical recommendations for pharmacogenetic testing.
基于基因型的华法林剂量算法是优化华法林剂量并降低药物不良反应的合理方法。不同人群,如非裔美国人和拉丁裔,对华法林剂量的需求存在更大的变异性,与欧洲血统的个体相比,他们发生华法林相关不良反应的风险更高。尽管这些数据表明,不同人群的患者可能受益于改进的华法林剂量估计,但基于基因型的华法林剂量的绝大多数文献,包括前瞻性随机试验的数据,都来自欧洲血统的人群。尽管种族/民族之间的变异频率不同,但大多数多样化人群的证据评估的都是在欧洲血统人群中最常见的变异。不包括跨越种族/民族群体重要变异的算法不太可能使多样化人群受益。在某些种族/民族群体中,开发特定种族或基于混合的算法可能会促进超越欧洲血统个体的基于基因型的华法林剂量指导算法的改进。在评估基于基因型的华法林剂量指导的临床实用性时,应该考虑到这些观察结果。在成功实施华法林药物基因组学方面,需要仔细考虑种族/民族,并针对改善跨种族/民族群体的华法林剂量算法提供更多证据。华法林药物基因组学的证据对华法林药物基因组学检测具有广泛的意义,强调在发现基因-药物对和制定药物基因组学检测的临床建议时考虑种族/民族。