Race and Pharmacogenetics discussed in the New England Journal of Medicine

The authors of a new Perspective in the New England Journal of Medicine (“Will precision medicine move us beyond race?”) focus on the potential pitfalls of using race based categories as proxies for pharmacogenetic variants. Self-identified race may not predict genotype or drug response in individual patients and the use of race as a proxy for ancestry and genetic variants is controversial and problematic. As an example of the power of precision medicine, and specifically pharmacogenetics, Bonham et al. discuss a 2014 lawsuit by the Hawaiian attorney general against the manufacturers of clopidogrel. The lawsuit claims that clopidogrel was marketed and sold to Hawaiians despite well-established studies showing that specific alleles in CYP2C19 (*2 and *3) compromise its efficacy and that those alleles are also known to be common in a significant proportion of Hawaii’s population (East Asian, Native Hawaiian and other Pacific Islanders). Bonham et al. believe that greater cohort diversity in prospective longitudinal drug studies will improve understanding of how genetic variability may affect drug response and safety between and within populations. In addition, they argue that sub-populations that respond best to targeted drug therapies would also benefit from these studies because the studies would provide the necessary evidence of therapeutic efficacy to justify the increased costs of treatment in those groups. Finally, evidence from such studies will be necessary to mobilize training resources for clinicians and health care systems so that they can incorporate pharmacogenetic information into routine dosing and prescribing decisions to ultimately improve treatment.  

More information about CYP2C19, and clopidogrel, including the FDA-approved drug label with annotated pharmacogenetic information can be found on PharmGKB. Dosing guidelines for CYP2C19 and clopidogrel are available on PharmGKB and CPIC.