Preventing the exacerbation of health disparities by iatrogenic pharmacogenomic applications: lessons from warfarin

The top genome-wide signals in the CYP2C9 region were rs9332238 (odds ratio: 6.8; p=4.4 ×10−13 ) and rs4917639 in the warfarin-treated Brazilians and Europeans cohorts, respectively (19,20). [...]the lead SNP in the VKORC1 locus of Brazilians was rs749671 (odds ratio: 20.4; p=1.08 ×10−33 ). A previous paper by Perini et al. showed that the VKORC1-1639G>A variant, also called 3673G>A, has frequencies ranging from 40 to 60% in three Native American populations of Brazil (26). Since Native Americans in Brazil comprise small groups that are often scattered across the entire country, allele frequencies published in a specific study should be observed with caution as they may not be representative of all Brazilian Native American and their allele frequencies may be significantly affected by genetic drift. [...]Suarez-Kurtzetal. argued that INR measurements are useful but cannot completely capture the information on dose variance provided by CYP2C9 and, particularly VKORC1 genotypes, the latter remaining the most informative predictor of stable warfarin dose requirements among Brazilians (27). [...]the guidelines recommend not using genotype-guided predictions in Blacks when CYP2C9 data lacks African-related alleles *5, *6, *8, *11.