The Future of Warfarin Pharmacogenetics in under-represented Minority Groups

Abstract

Genotype-based dosing recommendations are provided in the US FDA-approved warfarin labeling. However, data that informed these recommendations were from predominately Caucasian populations. Studies show that variants contributing to warfarin dose requirements in Caucasians provide similar contributions to dose requirements in US Hispanics, but significantly lesser contributions in African–Americans. Further data demonstrate that variants occurring commonly in individuals of African ancestry, but rarely in other racial groups, significantly influence dose requirements in African–Americans. These data suggest that it is important to consider variants specific for African–Americans when implementing genotype-guided warfarin dosing in this population.

Genotype frequencies of VKORC1 and CYP2C9 in Native and Mestizo populations from Mexico, potential impact for coumarin dosing

“…1A). The presence of a potential novel haplotype may support the notion that the most common haplotypes defined by Rieder do not completely capture all VKORC1 haplotypes, but rather a range of them (99-62%) depending on the ethnic group investigated (Cavallari and Perera, 2012).…”

“…Current knowledge on genes and genotypes that affect drug safety and efficacy have been mostly reported on Caucasian populations hence, the use of validated variants to tailor drug use cannot be freely extrapolated to other countries (Daar and Singer, 2005;Flockhart et al, 2009). Moreover, it is well recognized that native, Mestizos, or Hispanics in America are underrepresented in pharmacogenetic studies even more evidently than African Americans (Cavallari and P. MA, 2013). And although endeavors are currently ongoing, a complete characterization of the genetic diversity among diverse ethnic groups still encompasses a titanic task (Reich et al, 2012).…”

Personalized Medicine, Availability, and Group Disparity: An Inquiry into How Physicians Perceive and Rate the Elements and Barriers of Personalized Medicine

“…Individuals who metabolize warfarin slowly can build up dangerously high levels of warfarin if dosing is not carefully adjusted [31,32]. Commonly tested variants in CYP2C9 and VKORC1 are more prevalent in European Americans than in African Americans, while some variants are either more or less prevalent in Chinese individuals [33,34,35,36,37,38]. Furthermore, it has been shown that some variants are better at predicting dosage compared to other variants [32].…”

A Pharmacogenetics Service Experience for Pharmacy Students, Residents, and Fellows

“…24,25 Additional optional reading on warfarin pharmacogenetic dosing algorithms and genotypeguided warfarin dosing in minority populations was recommended. 7,8,26 The student, resident, or fellow and the faculty member spent time discussing the readings prior to applying them to patient care or research. Further, because most of the patients at the medical center were of minority descent, the faculty member devoted significant time to discussing the effect of ancestry on warfarin genetics, emphasizing the concepts of allele and genotype frequencies, haplotypes, and linkage disequilibrium.…”

“…24,25 Additional optional reading on warfarin pharmacogenetic dosing algorithms and genotypeguided warfarin dosing in minority populations was recommended. 7,8,26 The student, resident, or fellow and American Journal of Pharmaceutical Education 2013; 77 (8) Article 175.…”