Diet, environment, and lifestyle can all influence how a person responds to medicines — but another key factor is genes. The National Institute of General Medical Sciences (NIGMS) and other components of the National Institutes of Health (NIH) are sponsoring a nationwide research effort to understand how a person's genetic make-up determines the way a medicine works in his or her body, as well as what side effects the person might be prone to developing.

This so-called "pharmacogenetics" research focuses on linking the body's response to medicines with variations in particular genes. Many of these variations are expected to be "single-letter" differences, known as single-nucleotide polymorphisms or "SNPs." However, other genetic variations affecting how a person reacts to a specific medicine could be missing genes, or even extra genes. Through these types of studies, researchers ultimately hope to develop drug dosing into a much more predictive science.

"The outcome of pharmacogenetics research has the potential to improve the health of all Americans, by making the medicines of today and tomorrow safer and more effective for everyone," said Dr. Rochelle Long, a pharmacologist at NIGMS who spearheaded the pharmacogenetics initiative.

The trans-NIH effort is designed to forge an interactive research network of investigators who will store data in a shared information library freely accessible to the scientific community. To protect participants' privacy, names and other identifying information will not be stored in this library.

In addition to NIGMS, the other NIH components funding the pharmacogenetics research network awards are the National Cancer Institute (NCI); the National Heart, Lung, and Blood Institute (NHLBI); the National Human Genome Research Institute (NHGRI); the National Institute of Environmental Health Sciences (NIEHS); and the National Library of Medicine (NLM).

Nine awards, totaling $12.8 million for the first year of funding, have been made to:

• Stanford University School of Medicine in Palo Alto, Calif. (Russ B. Altman, M.D., Ph.D., principal investigator) — $1.6 million provided by NIGMS, NHGRI, and NLM to house and operate the Stanford Pharmacogenetics Knowledge Base (PharmGKB), which will serve as the shared information library for all scientists in the pharmacogenetics research network.]

• Brigham and Women's Hospital in Boston, Mass. (Jeffrey M. Drazen, M.D., principal investigator) — $2.6 million provided by NHLBI for a multicenter effort to discover which genes play a role in people's widely variable responses to the three main types of asthma treatments.

• Georgetown University Medical Center in Washington, D.C. (David A. Flockhart, M.D., Ph.D., principal investigator) — $1.3 million provided by NIGMS to investigate if and how genetic differences between people can explain the variable responses to tamoxifen, a widely prescribed drug used for cancer treatment and prevention.

• University of California, San Francisco (Kathleen M. Giacomini, Ph.D., principal investigator) — $3.2 million provided by NIGMS to study how drug response is affected by variability in the genes that encode cellular "gatekeeper" molecules called membrane transporters, which interact with a third of the most commonly used prescription drugs.

• University of California, Los Angeles (Julio Licinio, M.D., principal investigator) — $285,000 provided by NIGMS for a one-year pilot project to search for genetic differences that play a role in how Mexican-Americans respond to two different antidepressant drugs.

• Yale University in New Haven, Conn. (Prakash M. Nadkarni, M.D., principal investigator) — $421,000 provided by NIEHS to develop and implement a Web-based database tool designed to incorporate existing pharmacogenetic knowledge into the PharmGKB information library.

• University of Chicago (Mark J. Ratain, M.D., principal investigator) — $2.5 million provided by NIGMS and NCI for a multicenter effort to examine how the benefits, as well as the toxic side effects, of certain chemotherapy drugs vary among people.

• University of Houston Law Center in Houston, Tex. (Mark A. Rothstein, J.D., principal investigator) — $322,000 provided by NIGMS, NHGRI, and NIEHS to study the ethical, legal, and social implications of the use of pharmacogenetic information, paying particular attention to issues of race and ethnicity.

• The Mayo Foundation in Rochester, Minn. (Richard M. Weinshilboum, M.D., principal investigator) — $576,000 provided by NIGMS and NHGRI to exhaustively search for variations in genes encoding proteins already known to be important in the body's handling and disposal of a wide array of medicines, hormones, and chemical messengers.

NIH has announced its intent to solicit applications for the next round of pharmacogenetics research network awards. Applicants who devise the best plans for conducting pharmacogenetics research that will complement existing studies will join the network, and will contribute to the PharmGKB information library.

NIGMS funds research and research training in the basic biomedical sciences, including pharmacology, cell and molecular biology, and genetics. This support enables scientists at universities, medical schools, and research institutions throughout the country to expand knowledge about the fundamental life processes that underlie human health and disease.

Additional Resources

• This news release is posted on the NIGMS Web site at http://www.nigms.nih.gov/news/releases/pharmacogenetics.html.

• For more detailed information about the pharmacogenetics initiative, please consult information posted on the NIGMS Web site at http://www.nigms.nih.gov/funding/pharmacogenetics.html.

• An educational, lay-oriented brochure about pharmacogenetics entitled "Medicines for YOU" will be available shortly. To request a copy in English or Spanish, call the NIGMS Office of Communications and Public Liaison at 301/496-7301. An online, text-only version of the brochure is posted at http://www.nigms.nih.gov/funding/medforyou.pdf.

To arrange an interview with Dr. Rochelle Long, please contact Alison Davis at 301/496-7301.