Scientists Identify a Cause of Drug Metabolism Variations in Humans

St. Jude Children's Research Hospital (ALSAC)
Thursday, 29 March 2001

Discovery important for all ages, diagnoses and ethnic groups

(Memphis, Tennessee, March 29, 2001) 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 Hospitalâ . 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 Charitiesâ (ALSACâ ). 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.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org