What is Pharmacogenetics?

A person's environment, diet, and general state of health can all influence how he or she responds to medicines. But another key factor is genes. The study of how people respond differently to medicines due to their genetic inheritance is called pharmacogenetics. The term has been pieced together from the words pharmacology (the study of how drugs work in the body) and genetics (the study of how traits are inherited). An ultimate goal of pharmacogenetics is to understand how someone's genetic make-up determines how well a medicine works in his or her body, as well as what side effects are likely to occur. In the future, advances gleaned from pharmacogenetics research will provide information to guide doctors in getting just enough of the right medicine to a person--the practice of "personalized medicine."

Pharmacogenetics Research: The Road to Personalized Medicine
Before doctors can begin to dispense medications in such a personalized manner, much work must be done. A key task for pharmacogenetics researchers is to pinpoint all of the proteins that medicines encounter in the body and determine how these proteins vary from person to person. In the course of doing so, researchers must meticulously scrutinize the genes that code for these proteins to identify the basis for the protein differences. Scientists must also determine which genes contribute to diseases such as cancer, heart disease, or asthma. Identifying such genes will provide scientists with an arsenal of good targets for future medicines.

Studying Genes
Some pharmacogenetics researchers study many different genes, with no preconceived notions about their role in drug response. In this scenario, scientists are simply searching for ever-so-slight genetic differences. The vast majority (99.9 percent) of all human DNA is identical from person to person. Only one-tenth of a percent is unique. Yet these small DNA differences are a major determinant of who we are--why we can look and act so differently, how our bodies metabolize medicines, and the diseases to which we're prone. One type of a slight genetic difference between people is called a single nucleotide polymorphism, or "SNP." For reasons scientists don't fully understand, certain genes contain much more "natural" variation--and thus many more SNPs--than others.

Why does it matter? It may be that certain SNPs are the signature of "sensitivity" to a certain medicine, or even the harbinger of disease. For example, one particular protein in the body--an enzyme that chews up dietary fats--has been linked to heart disease. The gene that codes for this particular protein also happens to be loaded with SNPs. Scientists can't be sure that any or all of the SNPs in this gene, or any other, signal disease susceptibility. Carefully conducted research is the only good way to make or break these suspected links.

Studying Cells
Another way scientists might ask and answer questions about pharmacogenetics is by using animal and cell models. Genetically engineered mice, or cells grown in petri dishes, are popular tools for researchers. In this type of approach, scientists introduce the equivalent of spelling changes into the DNA of genes they want to study and then incorporate the altered genes into experimental cells or animals. Such researchers then look to see what, if any, changes occurred in the mice's physiology, or in the growth characteristics of the cell cultures, as a result. Such approaches often yield clues toward identifying targets for medicines in people.

Studying People
Finally, pharmacogenetics researchers can go about identifying targets for medicines by studying the genes of a collection of people--a family, a group of patients, or unrelated individuals--who respond to a medicine in an unusual or distinctive way. Perhaps these people's bodies break down a medicine very quickly or very slowly, compared to others. Clues to why these people respond in a particular way to medicines might be revealed by searching for variations in the DNA of each member of that group. Ultimately, it may be that these individuals possess a specific form of a protein involved somehow in the "handling" of drugs.

A vivid, real-life example of this is the response of cancer patients to a particular anti-leukemia drug. Some of these patients, many of whom are young children, break down, or "metabolize," this drug very quickly and thus require extra medicine to stem the growth of their cancer. Others metabolize the drug very slowly--these patients should be prescribed much less medicine, because anti-leukemia drugs can have dangerous side effects, and can even kill them. Pharmacogenetics research has shown that a simple blood test given to these patients ahead of time--in which a laboratory can "read" the sequence of a particular defective gene involved in drug metabolism--can accurately predict how much medicine they should receive.

NIGMS' Role in Supporting Pharmacogenetics Research
The National Institute of General Medical Sciences (NIGMS) is leading an NIH effort to encourage pharmacogenetics research. Part of this effort involves allocating money to fund large, collaborative research groups that will conduct pharmacogenetics studies. NIGMS is also encouraging the development of a public database that will contain the fundamental pharmacogenetics results from such research studies.

The main purpose of this pharmacogenetics public database is to help scientists match up genetic variations ("genotypes") with functional outcomes ("phenotypes"), such as which medicines work or don't work for certain people. As a data "library" of sorts, the database will be a very important tool for future research and medical treatment.

The National Institute of General Medical Sciences is one of the National Institutes of Health in the U.S. Department of Health and Human Services. By supporting basic biomedical research and training nationwide, NIGMS lays the foundation for advances in disease diagnosis, treatment, and prevention.