Using the VAP Cholesterol Test from Atherotech, Inc., University of Maryland researchers have found an association between a rare gene mutation and heart protection.
The information reported in a recent study could help in the development of heart disease risk-lowering drugs and also demonstrates the value of advanced lipid profile testing in the identification of individuals at increased risk of heart disease.
The genome-wide association study (GWAS) of fasting and postprandial triglyceride levels was performed as part of the Heredity and Phenotype Intervention (HAPI) Heart Study. The results, published in the highly respected journal, Science, identified a specific gene mutation (APOC3 R19X) present in 5 percent of a Lancaster County, Pa., Amish community. This rare genetic occurrence prevents the production of a protein (apoC-III) that leads to increased rates of atherosclerosis.
Toni I. Pollin, Ph.D., assistant professor of medicine at the University of Maryland School of Medicine and the triglyceride study's lead investigator, said participants who were carriers of the mutation had one of their inherited APOC3 genes "switched off," apparently resulting in several cardiovascular benefits. The benefits included low triglycerides and LDL (bad cholesterol) levels, high HDL (good cholesterol) levels and protection against heart disease as evidenced by decreased levels of coronary artery calcification.
The association between these improved lipid profiles and decreased coronary artery calcification - an underlying indicator of coronary heart disease - was confirmed using the expanded cholesterol profiling capabilities of the VAP (Vertical Auto Profile) Test.
"Using the VAP profile, we were able to demonstrate that mutation carriers have extraordinarily low levels (less than 50 percent of normal) of remnant lipoproteins, which are highly atherogenic particles generated during the absorption and clearance of triglycerides derived from dietary fat," Dr. Pollin noted.
Lipid-lowering fibrates actually work in part through decreased APOC3 expression. Other lipid-lowering therapies such as statins, niacin, ezetimibe, fish oil and weight loss have also been associated with decreases in apoC-III protein levels. Dr. Pollin believes the next step is the discovery of new therapies aimed specifically at blocking apoC-III expression, improving lipid profiles and decreasing the risk of heart attack and stroke.
Dr. Pollin's study was conducted on 809 Old Order Amish individuals as part of the University of Maryland School of Medicine's HAPI Heart Study, which was designed to identify genetic factors in response to short-term interventions related to cardiovascular risk. The GWAS allowed researchers to rapidly scan 500,000 markers in the DNA of the participants to find variations that are associated with triglyceride levels in the blood.