Event Title

Promoting Diversity in Pharmacogenetics by Analyzing Genetic Variation Data with Respect to Metabolite Formation from African American-donor-derived Hepatocytes

Session Number

Project ID: MEDH 17

Advisor(s)

Dr. Minoli Perera, Carolina Clark, Northwestern University

Discipline

Medical and Health Sciences

Start Date

20-4-2022 10:45 AM

End Date

20-4-2022 11:00 AM

Abstract

Pharmacogenomics is being increasingly used to guide certain clinical prescription decisions and will feed into future precision medicine applications. However, current pharmacogenetics (PGx) studies (and thus, the clinical guidelines coming out of PGx studies) are done predominantly using subjects of European descent and thus not representative of the human population. CYP function can be very different between ethnicities, and thus basing clinical studies/guidelines on one ethnicity undermines the application to all populations. Our project began by isolating hepatocytes from African-American liver donors; each donor was genotyped. The hepatocytes were used in a cell culture experiment where 6 clinically relevant probe-drugs were dosed in vitro and over the course of four hours, we took several time points and measured the accumulation of metabolite for each drug using LC-MS. We calculated a rate of metabolite formation to determine if these rates were associated with genetic variation through GWAS (Genome-Wide Association Studies). Through the work we are currently conducting, we are able to contribute valuable data for minority populations. The inclusion of these populations is vital because it helps us improve the accuracy of the representation of diverse populations in precision medicine.

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Apr 20th, 10:45 AM Apr 20th, 11:00 AM

Promoting Diversity in Pharmacogenetics by Analyzing Genetic Variation Data with Respect to Metabolite Formation from African American-donor-derived Hepatocytes

Pharmacogenomics is being increasingly used to guide certain clinical prescription decisions and will feed into future precision medicine applications. However, current pharmacogenetics (PGx) studies (and thus, the clinical guidelines coming out of PGx studies) are done predominantly using subjects of European descent and thus not representative of the human population. CYP function can be very different between ethnicities, and thus basing clinical studies/guidelines on one ethnicity undermines the application to all populations. Our project began by isolating hepatocytes from African-American liver donors; each donor was genotyped. The hepatocytes were used in a cell culture experiment where 6 clinically relevant probe-drugs were dosed in vitro and over the course of four hours, we took several time points and measured the accumulation of metabolite for each drug using LC-MS. We calculated a rate of metabolite formation to determine if these rates were associated with genetic variation through GWAS (Genome-Wide Association Studies). Through the work we are currently conducting, we are able to contribute valuable data for minority populations. The inclusion of these populations is vital because it helps us improve the accuracy of the representation of diverse populations in precision medicine.