Kaiser Permanente, one of the nation’s largest health systems, conducted a real-world study to find that neurological side effects from phenytoin, an anti-seizure medication, are more common in patients with certain genetic variants. Interestingly, the same genetic also correlated with lower adherence to treatments leading researchers to suspect they may play a role in patients finding the right medication.
Jan Greene writing for Kaiser noted that the study was published August 30 in the journal Pharmacogenetics and Genomics and affirmed the previously identified association between specific genetic variants and phenytoin blood concentrations. Ms. Greene points out that variants of the CYP2C9 gene can cause patients receiving the same dose of phenytoin to experience blood levels of the drug that fluctuate too high or too low.
The Kaiser Permanente investigators used genetic data collected from more than 100,000 Kaiser Permanente Northern California (KPNC) consenting patients. They agreed to fill out a survey and share blood or saliva from which their genotype was mapped. The investigators uncovered that patients with the lowest predicted activity of the CYP2C9 gene were more than twice as likely to experience neurologic side effects, such as slurred speech and loss of balance. The same patients were twice as likely not to take their medications due to the side effects.
The lead investigator, Alison Fohner reported: “This is the first big real-world view of how phenytoin pharmacogenetics is affecting patients in mainstream care.” She continued “This kind of research in health systems like Kaiser Permanente is vital to moving the field forward.”
The Clinical Pharmacogenetics Implementation Consortium (CPIC) 23 Guidelines of Gene-Drug Combinations
CPIC currently lists 23 guidelines on gene-drug combinations with enough evidence to influence clinical practice. The CYP2C9/phenytoin combination is included in the list—hence why the Kaiser Permanente team selected it for analysis. CPIC will update its recommendation for phenytoin dosing in the near future reports Ms. Greene. Ms. Fohner articulated that this study will impact the updating of the CPIC guidelines.
Kaiser Permanente Research Bank (KPRB)
The study utilized de-identified patient genetic data from the Resource for Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, which is now part of the Kaiser Permanente Research Bank (KPRB). This research bank has grown to include data from more than 340,000 Kaiser Permanente consenting volunteering their health information, maintained securely and without revealing names. KPRB is actively recruiting volunteers among Kaiser Permanente members to share samples and other health information.
Call to Action: If you are a Kaiser Permanente member contributing to the KPRB only enriches the data for future studies that will help all. Interested in partnering with Kaiser Permanente for the usage of KPRB? Why not contact them to learn more.