The genetic basis for why some people do not express, or produce, CYP3A5, a specific protein that helps the body metabolize one half of all drugs, including many anti-cancer drugs and organ rejection drugs, has been identified by researchers at St. Jude Children's Research Hospital®. This genetic mutation impacts a larger percentage of patients than previously believed. The study results are published in the April issue of Nature Genetics.
The St. Jude team, led by Erin Schuetz, Ph.D., found that, compared to
people who express CYP3A5 protein, those persons who do not express, or
produce, the CYP3A5 protein may experience altered drug response or toxicity
when given drugs metabolized by CYP3A5.
Because the frequency of the genetic mutation affecting CYP3A5 expression
differs between ethnic groups, various ethnic groups may respond differently
to drugs handled by the 3A5 protein. Researchers studied human liver and
intestine tissue samples, the organs primarily responsible for drug
metabolism. The results indicated that only 25 percent of Americans from
European descent produce this protein while over 50 percent of Asians and
African-Americans produce the protein.
Based on these findings, the team predicts many patients will eventually
be genetically tested to see if they have the ability to express 3A5 and that
guided by CYP3A5 genotype, it is likely a large percentage of future patients
will receive dose adjustments of cancer chemotherapies and organ rejection
drugs to eliminate toxicity and improve therapeutic response.
St. Jude Children's Research Hospital, in Memphis, Tenn., was founded by
the late entertainer Danny Thomas. The hospital is an internationally
recognized biomedical research center dedicated to finding cures for
catastrophic diseases of childhood. The hospital's work is supported through
funds raised by the American Lebanese Syrian Associated Charities®
(ALSAC®). All St. Jude patients are treated regardless of their family's
ability to pay. ALSAC covers all costs of treatment beyond those reimbursed
by third party insurers, and total costs for families who have no insurance.
Dr. Schuetz's study was also funded by the National Institute of General
Medical Sciences, a component of the National Institutes of Health. NIGMS has
recently launched a major research effort into studying pharmacogenetics, the
science of how genes affect people's responses to medications. A free
educational brochure is available at