Researchers at the University of Maryland School of Medicine in Baltimore 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 help prevent cardiovascular disease.
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 of the APOC3 gene 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 having a lifelong deficiency of apoC-III helps to protect people from developing cardiovascular disease," she says.
Triglycerides and cholesterol are lipids, or fats that circulate in the blood. ApoC-III is a protein that is bound to circulating lipids. It inhibits the breakdown of triglycerides so they stay in the blood longer. Elevated levels of apoC-III are associated with higher triglyceride levels.
"The discovery of this mutation may eventually help us to develop new therapies to lower triglycerides and prevent cardiovascular disease," Dr. Pollin says. This is the first reported mutation within the human APOC3 gene that specifically blocks the production of apoC-III, causing individuals who carry a copy of the mutation to produce half the typical amount of the protein.
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. This was followed by direct gene sequencing. The GWAS technique is being used widely by scientists around the world to track down genes associated with many diseases.