An introduction to pharmacogenomics - UB Reporter

An introduction to pharmacogenomicsBy CHARLOTTE HSU
Published: June 10, 2010

In a presentation titled "The Genomics Revolution and Personalized Medicine," Daniel Brazeau, director of the Pharmaceutical Genetics Laboratory, introduced an audience of more than 100 people to the burgeoning field of pharmacogenomics, which seeks to tailor treatments for diseases to a patient's genetic makeup and the specific disease conditions of each patient.

"I believe that genomics is going to revolutionize the field of medicine and health care, but there's a considerable amount of hype associated with it," Brazeau said in opening his hour-long public lecture. His talk was the second in this year's UBThisSummer series, which takes place every Wednesday, through July 28, in the Natural Sciences Complex, North Campus.

Brazeau, a research associate professor in the Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, said while pharmacogenetics will contribute to greatly improved therapeutics, successes hinge on a realistic understanding of the complexity of the human genome, which contains about 3 billion DNA base pairs. These base pairs—the nucleotides thymine, guanine, cytosine and adenine—are the building blocks of genes, which are responsible for coding all proteins in the human body.

The gene that serves as the blueprint for insulin is 17,000 base pairs long. The longest gene sequence in the human genome contains 2 million base pairs and codes for the protein dystrophin.

Differences in individuals' genetic makeup arise through DNA replication in the reproductive process, during which base pairs may be deleted, inserted or substituted by mistake. In some cases, whole genes are duplicated. Because so much of a human's genetic material does not code for any protein, such copying errors might have no effect on a person's well-being.

Certain variations, however, can have an enormous impact on health. An individual's genetic makeup can, for instance, change the way a particular drug works in his or her body.

Take codeine: In humans, the enzyme cytochrome P450 2D6 (CYP2D6) converts codeine into morphine, which provides pain relief. And it just so happens, Brazeau said, that a fraction of the human population—about 10 percent of Caucasians, for example—lacks a functional copy of the gene that codes for CYP2D6. These patients are called "poor metabolizers."

A smaller number of people are "ultra-metabolizers," with multiple copies of the CYP2D6 gene, enabling them to process codeine into morphine at an elevated rate, which can lead to problems including impaired respiration and sedation. In a few cases, babies of ultra-metabolizer mothers have died from morphine overdoses after breastfeeding.

The codeine issue raises an ethical dilemma, Brazeau said: Given such variations in CYP2D6 production, should hospitals routinely test new mothers for the CYP2D6 gene? Such large-scale screening would be expensive for the nation’s health care system, and very few individuals possess multiple copies of the gene in question.

Besides affecting the way in which a person responds to a drug, genetic information can help to individualize disease. Scientists have found that in some breast cancer patients, over-expression of the gene that produces Human Epidermal growth factor Receptor 2 (HER2) is the root cause of the disease, with HER2 encouraging tumor cells to grow and divide more quickly. In women who test positive for this variation, the drug Herceptin helps treat cancer by binding to and blocking the activity of HER2.

The Her2 and CYP2D6 case studies demonstrate the power of pharmacogenomics. But each of these two examples also involves just one gene. A deeper understanding of the relationship between pharmaceuticals and the human genome will require increased study of the role that multiple genes and variants, along with environmental factors, play in predicting drug efficacy and toxicity in individuals, Brazeau said.

The promise of genomics is its ability to personalize disease, Brazeau said: to identify people or populations at risk, and, ultimately, to understand "what it means for a specific individual to have high blood pressure or cancer...There are a variety of causes for these diseases, and if we can identify the specific cause in a specific individual, then we can design new drugs."

The UBThisSummer lecture series takes place at 4 p.m. on Wednesdays in 225 Natural Sciences Complex, North Campus. Remaining lecture topics include:

• June 16: "Is Social Science Science?" Joseph Woelfel, professor, Department of Communication, College of Arts and Sciences.

• June 23: "Perverted Justice: Sex Offenders and the Law," Charles Patrick Ewing, SUNY Distinguished Service Professor, Law School.

• June 30: To Be Announced.

• July 7: A lecture by Aaron Hughes, Associate Director and Professor, Institute of Jewish Thought and Heritage.

• July 14: "From Understanding Volcanic Hazards to Preventing Their Disasters," Michael Sheridan, UB Distinguished Professor Emeritus, Department of Geology, College of Arts and Sciences.

• July 21: "Extracting Intelligence from Social Media Data," Rohini Srihari, associate professor, Department of Computer Science and Engineering, School of Engineering and Applied Sciences.

• July 28: "Toward the Bionic Human: Medical Devices and How They Are Powered," Esther Takeuchi, SUNY Distinguished Professor and Greatbatch Professor in Power Sources Research, School of Engineering and Applied Sciences.
open here to see the abstracts:
An introduction to pharmacogenomics - UB Reporter