Amish Gene Mutation Makes Them Immune to Heart Disease

Amish Gene Mutation Makes Them Immune to Heart Disease

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amish_man.jpgAfter a dozen studies of the Amish over 15 years, researchers at the University of Maryland School of Medicine have discovered a novel gene mutation among the Old Order Amish population that significantly reduces the level of triglycerides in the blood and appears to make them immune to cardiovascular disease.

The scientists believe the mutation was first introduced into the Amish community in Lancaster County by a person who was born in the mid-1700s. This mutation appears to be rare or absent in the general population.

Alan R. Shuldiner, M.D., the study’s senior author, says, “The Old Order Amish are ideal for genetic research because they are a genetically homogenous people who trace their ancestry back 14 generations to a small group that came to Pennsylvania from Europe in the mid-1700s.”The results of the study will be published in the Dec. 12, 2008, issue of the journal Science.

“We found that about 5 percent of the Amish have a gene mutation that speeds up the breakdown of triglycerides, which are fat particles in the blood associated with an increased risk of coronary artery disease,” says the lead investigator, Toni I. Pollin, Ph.D., an assistant professor of medicine at the University of Maryland School of Medicine. Carriers of the mutation have half the amount of apoC-III, a protein linked to triglycerides, than people without the gene variant.

Dr. Pollin says that those with this mutation have higher levels of HDL-cholesterol, the so-called “good” cholesterol, and lower levels of LDL-cholesterol, the “bad” cholesterol. In addition, they have less arteriosclerosis (hardening of the arteries) – as measured by the amount of calcium in their coronary arteries. “Our findings suggest that this deficiency helps to protect people from developing cardiovascular disease,” she says.

Triglycerides and cholesterol are lipids, or fats that circulate in the blood. The gene studied in the Amish inhibits the breakdown of triglycerides so they stay in the blood longer.

“The discovery of this mutation may eventually help us to develop new therapies to lower triglycerides and prevent cardiovascular disease,” Dr. Pollin says.

More than 800 members of the Old Order Amish community in Lancaster County, Pa., participated in the study, which was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Researchers used a new approach called a genome-wide association study, or GWAS, to rapidly scan 500,000 markers in the DNA of the participants to find variations, or single nucleotide polymorphisms called SNPs, that are associated with triglyceride levels in the blood. The GWAS technique is being used widely by scientists around the world to track down genes associated with many diseases.

As part of the study, participants drank a high-fat milkshake and then were closely monitored for the next six hours with blood tests as well as ultrasound tests of their brachial artery to determine how well their arteries were coping with the fatty meal. Some also were tested to determine if there were calcium deposits in their coronary arteries, which is a clear sign of cardiovascular disease. “What we found is that people who have the mutation are much less likely to have any calcification,” Dr. Pollin said.

The study is part of a larger University of Maryland research project, the Heredity and Phenotype Intervention (HAPI) Heart Study, which examined how genes and lifestyle factors influence the risk of developing cardiovascular disease.

Since 1993, Maryland researchers have searched for genes in the Amish that cause a variety of medical problems, such as type 2 diabetes, obesity, osteoporosis and high blood pressure. “We have uncovered a wealth of information in our studies of the Amish over the years, and much of what we have found is not only applicable to this unique population, but the general public as well,” Shuldiner says.

Dr. Shuldiner is a professor of medicine; head of the Division of Endocrinology, Diabetes and Nutrition; and director of the Program in Genetics and Genomic Medicine at the University of Maryland School of Medicine.  The results of the study will be published in the Dec. 12, 2008, issue of the journal Science.

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