Warfarin Pharmacogenomics in Diverse Populations

Abstract

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 warfarinrelated 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.

Genetic Ancestry Analysis Reveals Misclassification of Commonly Used Cancer Cell Lines

“…For example, an admixed individual with 20% EUR genetic ancestry may be at greater or lesser risk of certain diseases than an individual with 40% EUR genetic ancestry (56)(57)(58)(59)(60). In addition, the implications for pharmacogenomics exist as the nuances of drug effects or mechanisms may not be generalizable in the African American population due to high WA genetic variance (28,61). For these reasons, there remains a burden on the scientific community to expand the collection of currently available human cell lines by incorporating more non-European options to capture the complete picture of genetic contribution to disease incidence, aggressiveness, progression, and response to treatment.…”

Leveraging the learning health care model to improve equity in the age of genomic medicine

“…Genomic integration into EHRs therefore comes with both significant caveats and substantial opportunity. On the one hand, care must be taken to assess the utility of genomic testing and the meaning of genomic results in specific contexts . On the other, the nature of EHRs and the facility with which they can be analyzed as a dataset allows health care systems to evaluate the effects of genetically enabled care on health outcomes, which have the potential to add not only to the improvement of patient care directly, through the refinement of clinical practices, but also indirectly through enhancement of the body of knowledge upon which biomedical discovery and development is based .…”

“…On the one hand, care must be taken to assess the utility of genomic testing and the meaning of genomic results in specific contexts. 11,[13][14][15][16] On the other, the nature of EHRs and the facility with which they can be analyzed as a dataset allows health care systems to evaluate the effects of genetically enabled care on health outcomes, which have the potential to add not only to the improvement of patient care directly, through the refinement of clinical practices, but also indirectly through enhancement of the body of knowledge upon which biomedical discovery and development is based. 17 In so doing, these health care systems can shed light on gaps in our scientific knowledge and ---This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.…”

Do Patients With High CHA₂DS₂-VASc Scores Need High Intensity of Anticoagulants After Valve Surgery?

“…18,23, 24 Another potential explanation is the polymorphism of pharmacogenetics such as CYP2C9, CYP4F2, and VKORC1 genetic variants. 25 According to previous studies, the total variability in warfarin dose explained by CYP2C9*3, VKORC1-1639G>A, and CYP4F2*3 is estimated at 40-63% in the Asian population. 26 Furthermore, a higher number of genetic variants predisposing individuals to VTE is found in Europe and America than in Asia.…”