Five-year project expands Dr. Alan Shuldiner’s work with Old Order Amish in Pa.
Alan R. Shuldiner, M.D., a diabetes researcher and director of the Program in Human Genetics at the University of Maryland School of Medicine, has received a five-year, $7.5 million grant from the National Institutes of Health (NIH) to search for genes that might predict how a person responds to medications commonly used to treat and prevent cardiovascular disease. The goal of such pharmacogenomics research is to help tailor medicines to people’s unique genetic characteristics.
Dr. Shuldiner will recruit 600 members of the Old Order Amish community in Lancaster County, Pa., to take part in the study to assess how well two drugs – Plavix (clopidrogel bisulfate) and aspirin – work to prevent platelets from sticking together and producing blood clots which can cause heart attacks and strokes. The participants have already undergone extensive genetic testing as part of another cardiovascular study underway at Dr. Shuldiner’s research clinic in Strasburg, Pa.
“We will give the volunteers the drug Plavix alone and combined with aspirin, and then measure their platelet function before and after receiving these medications. Some people will respond well while others will not,” Dr. Shuldiner explains. “Then, we will search the entire genome, performing 500,000 different tests using DNA from all 600 participants, trying to locate specific chromosomal regions and genes shared by those who responded well to these anti-platelet agents,” he says.
Dr. Shuldiner, professor and head of the Division of Endocrinology, Diabetes and Nutrition at the University of Maryland School of Medicine, has studied the Amish since 1993, looking at health problems, such as diabetes, obesity, osteoporosis and high blood pressure, as well as why many members of the community live long into their 90s. More than 3,000 Old Order Amish have taken part in these studies.
This latest project is being funded by the National Institute of General Medical Sciences. Dr. Shuldiner is a member of the Pharmacogenetics Research Network, a nationwide collaboration of scientists supported by the NIH to study how a person’s genes affect the way he or she responds to medicines. The goal is to help tailor drug prescriptions to an individual’s genetic make-up and to make medicines safer and more effective for everyone.
“Pharmacogenomics is a field in which we are trying to find out why there is such a wide variation in individual responses to drugs, not only whether a drug is beneficial or not, but also whether a person is susceptible to various adverse side effects. That information could be used to provide the most effective therapy for a given patient. We are developing the concept of individualized medicine,” Dr. Shuldiner says.
He notes that the Old Order Amish in Lancaster County, Pa., are ideal for genetic studies because they are a genetically homogenous people, tracing their ancestry back 14 generations to a small group who came to the United States from Europe in the mid-1700s. The Amish also have large families, keep detailed genealogical records and have a similar rural lifestyle.
In 2002, Dr. Shuldiner received a four-year, $10.6 million NIH grant to study how genes and lifestyle factors influence people’s risk of developing cardiovascular disease. He and his team are measuring how 1,000 Amish volunteers respond to four interventions: a high-fat meal, a high- and low-salt diet, aspirin and exposure to extreme cold to evaluate the effect on their blood vessels.
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