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.

Figure 1. Genes affecting warfarin

Pharmacokinetics (shown in oval boxes) and pharmacodynamics (shown in rectangular boxes).

Figure 2. Median warfarin dose requirements by VKORC1 -1639G>A and 1173C>T genotypes in Caucasians and African–Americans, according to data from the International Warfarin Pharmacogenetics Consortium

Data taken from [26].

Figure 3. Median warfarin dose requirements by race and ethnicity

Data taken from [26,33].

Figure 4. Median (range) warfarin dose requirements in African–Americans with the CYP2C9*1/*1 genotype compared with CYP2C9*8 allele carriers and carriers of a CYP2C9*2, *3, *5, *6 or *11 allele

Lines within boxes represent medians. Lower and upper borders of the boxes represent 25th and 75th percentiles, respectively. Whiskers below and above boxes represent 10th and 90th percentiles, respectively. NS: Not significant. Data taken from [21].