How do patients' genes affect the choice of these drugs?

How do patients' genes affect the choice of these drugs?

Kaiser Permanente's analysis found that the neurological side effects of the anticonvulsant drug phenytoin are more common in patients with certain genetic variants. The same genetics have also been associated with lower adherence to treatment, suggesting that they may play a role in patients finding the right medications.

A study published in Pharmacogenetics and Genomics on August 30 confirmed a previously identified association between specific genetic variants and phenytoin blood levels. CYP2C9 & gene variants may cause blood levels of the drug to be too high or too low in patients receiving the same dose of phenytoin.

Research Assistant Alison Fohner, PhD, who is also an Assistant Professor of Epidemiology at the University of Washington

The researchers also looked at electronic patient data and found that genetic variation could affect health care in surprising ways; patients may not take the medication as prescribed and may find it more difficult to find the ideal medication and dose, leaving them vulnerable to uncontrollable seizures.

This suggests that patients and physicians may respond to patients' pharmacogenetic variants even without knowledge of their specific genetics. study time.

"This is the first major real-world view of how phenytoin pharmacogenetics affects patients in routine care," said Fohner, an assistant professor of epidemiology at the University of Washington. "Research in health systems such as the Kaiser Permanente is crucial to moving the field forward."

The study used genetic data from more than 100,000 Northern California Kaiser Permanente (KPNC) patients who agreed to complete the study and share a blood or saliva sample from which the genotype was mapped. The researchers found that patients with & nbsp; CYP2C9 & # 39; gene had the lowest predicted activity, neurological side effects such as blurred speech and loss of balance were more than twice as likely. These same patients were almost twice as likely to not take the medicine as expected, due to potential side effects.

Catherine Schaefer, PhD, Researcher, Research Department

The research does not provide specific clinical advice to physicians, as it would be unusual for them to have extensive genetic information about patients, said senior Author Catherine Schaefer, PhD, researcher at Kerman's Permanente Research Department and executive director of the Foundation. gene, environment and health research program. This study shows that prescribing effective, safe and tolerable drugs can provide important information about genetic variants of drug metabolism genes, he added.

"There are many factors that doctors consider in deciding which medication to prescribe and at what dose," Schaefer said. "Knowing if a patient has a genetic variant that causes higher or lower blood levels of a drug could be useful information to balance the pros and cons of prescribing a particular drug at the usual dose."

Fohner said the study provides a valuable picture of what genetics can mean for patients receiving treatment for frightening and often chronic diseases. The longer these patients take effective therapy, the longer they are at risk of serious side effects or persistent seizures, and the more frustrating their treatment is the odyssey. "The more information needed to have the best medicine and the best dose for these patients, the better," he said. "Genetics helps us do that."

The Consortium for the Application of Clinical Pharmacogenetics (CPIC) currently lists 23 gene drug combination guidelines with sufficient evidence to influence clinical practice. This list contains & nbsp; The CYP2C9 / phenytoin combination, so the researchers chose it for analysis, Fohner said. The CPIC is expected to update its phenytoin dosing recommendation soon. Fohner said that as this is the largest study of the pharmacogenetics of phenytoin to date, it will play an important role.

This study used genetic data from de-identified patients in the Adult Health and Aging Genetic Epidemiology Research Resource (GERA) cohort, which is now part of the Kaiser Permanente Research Bank (KPRB). The research bank contains data from more than 340,000 Kaiser Permanente members who have voluntarily provided their health information, which is kept safe and anonymous. KPRB will continue to actively recruit volunteers from Kaiser Permanente to provide samples and health information.

The initial development of the KPNC GERA cohort was funded by the Robert Wood Johnson Foundation, the Wayne and Gladys Valley Foundation, the Ellison Medical Foundation, the Kaiser Permanente community support programs, and support from national health institutes. This study was supported by the Kaiser Permanente Delivery Science Fellowship Program and the Kaiser Permanente Research Healthcare Delivery and Policy Research Department.

Other authors included MD, MSc, Vincent Liu, PhD, Brian L. Lawson, Dilrin K. Ranatunga, and Khanh K. Thai, MS, from Kaiseri Permanente Research Department; Aline T. Jelalian, MD, Kaiser Permanente of the Northern California Department of Neurology; Allan E. Rettie, Ph.D., Department of Medicinal Chemistry, University of Washington; and Neil Risch, PhD, & nbsp; and Akinyemi Oni-Orisan, PharmD, PhD, Institute of Human Genetics, University of California, and University of California, San Francisco, Department of Clinical Pharmacy.

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