Genes' influence on common drugs may affect health-care quality, cost

Jan. 4, 2006 -- Chances are good that a medication you take is one of several drugs that can be affected by genetic factors, according to researchers at Washington University School of Medicine in St. Louis and the St. Louis College of Pharmacy. They found that 29 percent of patients seen at local primary-care offices had taken at least one of 16 drugs that can cause adverse reactions in genetically susceptible people.

Finding that so many primary-care patients use such medications suggests that pharmacogenetics—the study of the interplay between genes and drugs—has the potential to benefit a large portion of the population, according to the researchers. Applying information from pharmacogenetics to primary-care practices could reduce the incidence of adverse reactions and optimize treatments, according to the study, published in the January 2006 issue of the journal Pharmacogenomics.

"Until now, researchers looking at the role of genetic variation in drug effects have focused mainly on toxic drugs used by specialists treating cancer or HIV infection," says Howard L. McLeod, Pharm.D., director of the pharmacology core at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. "We knew that some of the drugs commonly used in the family practice setting can cause adverse reactions in people who have certain genetic variations, so we measured just how often these drugs are used."

The study found that of the 607 outpatients surveyed at three primary-care sites in the metropolitan St. Louis area, 174 were on a drug commonly associated with severe side effects. Among these drugs are fluoxetine (Prozac™), metoprolol (a beta-blocker), diltiazem (used to treat high blood pressure), and warfarin (an anticoagulant).

Each of these drugs is metabolized by genes known to vary within the population. Genetic variations that change the properties of enzymes that break down drugs or mark them for excretion can cause adverse drug reactions.

Potentially harmful reactions to the medications examined in this study include gastrointestinal bleeding, cerebrovascular hemorrhages, kidney impairment, dizziness, low blood pressure and slowed heart beat. The number and severity of adverse reactions to the drugs surveyed was not measured in this study; however, a 1998 study ranked adverse drug reactions as among the top ten leading causes of death in the United States.

Other genetic variations in the population are known to alter proteins that transport drugs or change cellular mechanisms targeted by drugs, rendering the drugs ineffective. While not leading to adverse reactions, these genetic factors can also affect health care.

"We think it's likely that using pharmacogenetics in the primary-care setting can reduce health care costs," says McLeod, who is also professor of medicine, of genetics, and of molecular biology and pharmacology at the School of Medicine. "The information could help family physicians make better decisions about the right drugs and dosages to prescribe for their patients, making it possible to avoid unnecessary prescriptions and to minimize the costs of hospital treatments for adverse reactions."

In an editorial in the same journal, Deepak Voora, M.D., chief medical resident, and Brian F. Gage, M.D., associate professor of medicine, assert that guidance from primary-care physicians will be important to winning patients' acceptance of the genetic testing necessary to apply pharmacogenetics to family care practice.

"The primary-care physician is the main advocate for the patient and who patients will look to for advice about pharmacogenetics testing," Voora says. "The way they handle pharmacogenetic information can alleviate patients' fears concerning privacy and access to medical records by employers and insurance agencies."

Grice GR, Seaton TL, Woodland AM, McLeod HL. Defining the opportunity for pharmacogenetic intervention in primary care. Pharmacogenomics, 2006 Jan;7(1):61-65.

Voora D, Gage BF. Is primary care ready for pharmacogenetics? Pharmacogenomics, 2006 Jan;7(1):1-3.

Funding from the National Institutes of Health supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Siteman Cancer Center is the only NCI-designated Comprehensive Cancer Center within a 200-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine.