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Genetics and Genomics
Session Title: Genetic Epidemiology, Genomics, and Pharmacogenomics II

Abstract 16081: Frequency of Potentially Clinically Relevant Variants of CYP2C19 And SLCO1B1 in a Large Direct-to-Consumer Genetic Database

Originally publishedCirculation. 2019;140:A16081

    Introduction: Pharmacogenetic testing holds great potential for supporting clinical decision making and optimizing medication outcomes. CYP2C19 and SLCO1B1 are two examples of cardiovascular pharmacogenes with the evidence supporting implementation in clinical practice. However, the clinical uptake of pharmacogenetic testing has been slow. Recent FDA authorization for a direct-to-consumer (DTC) pharmacogenetic test will improve access to pharmacogenetic testing. This study aims to characterize the frequency of four variants CYP2C19 (*2, *3, and *17) and SLCO1B1 (*5) in a generally unselected group of genotyped individuals who have used DTC genetic testing (23andMe, Inc. Mountain View, CA).

    Methods: Participants were genotyped between 2013 and 2019 using Illumina genotyping arrays that included the CYP2C19*2 (c.681G>A, rs4244285), *3 (c.636G>A, rs4986893), and *17 (c.-806C>T, rs12248560), and SLCO1B1*5 (c.521T>C, rs4149056) variants. Eligible subjects were 23andMe U.S. customers who were > 18 years of age and consented to participate in research. IRB approval was obtained from Ethical & Independent Review Services.

    Results: More than 80% of genotyped individuals consented to participate in this study. Out of approximately 3.5 million eligible participants included in this analysis, the overall variant frequencies of CYP2C19 *2, *3, and *17 were 15.4%, 0.3%, and 20.2%, respectively. The overall variant frequency of SLCO1B1*5 was 15.0%. Frequencies of actionable phenotypes (translation of variant/diplotypes to predicted phenotypes) and stratification of variant frequencies by ethnicity are underway and will be presented.

    Conclusions: Approximately 70% of genotyped participants had at least one potentially clinically relevant variant in CYP2C19 or SLCO1B1. Nearly 60% of genotyped participants had at least one of the three tested CYP2C19 variants and 28% had the SLCO1B1 variant. These findings suggest that preemptive DTC pharmacogenetic testing can be used to disseminate potentially clinically useful information to a large number of consumers and facilitate conversations with their healthcare providers about implications for their current and future therapies.


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