Rare Gene Mutations That may Prevent Heart Disease Discovered

In the apolipoprotein B (APOB) gene, protein-truncating variants were found to be associated with lower triglyceride and LDL cholesterol levels. The protein-truncating variants were also linked to lower the risk of coronary heart disease by 72 percent, according to a new study co-led by a Boston University School of Public Health (BUSPH) researcher. Published in the journal Circulation: Genomic and Precision Medicine.

Protein-truncating variants in the APOB gene are among the causes of a disorder called familial hypobetalipoproteinemia (FHBL), which causes a person's body to produce less low-density lipoproteins (LDL) and triglyceride-rich lipoproteins. People with FHBL generally have very low LDL cholesterol, but are at high risk of fatty liver disease. "An approved drug, Mipomersen, mimics the effects of having one of these variants in APOB, but due to the risk of fatty liver disease, clinical trials for cardiovascular outcomes won't be done," says study co-lead author Dr. Gina Peloso, assistant professor of biostatistics at BUSPH. "Using genetics, we provided evidence that targeting this gene could reduce the risk of coronary heart disease."