Rare Gene Mutations May Prevent Heart Disease.
A kind of rare gene mutation may prevent heart disease, according to a new study co-led by a School of Public Health researcher.
The study, published in the journal Circulation: Genomic and Precision Medicine, finds that protein-truncating variants in the apolipoprotein B (APOB) gene are linked to lower triglyceride and LDL cholesterol levels, and lower the risk of coronary heart disease by 72 percent.
These APOB variants 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 Gina Peloso, the study’s co-lead author and an assistant professor of biostatistics. “Using genetics, we provided evidence that targeting this gene could reduce the risk of coronary heart disease.”
For the study, the researchers sequenced the APOB gene in members of 29 Japanese families with FHBL. They also sequenced the APOB gene in 57,973 participants of a dozen coronary heart disease case-control studies of people with African, European, and South Asian ancestries, 18,442 of whom had early-onset coronary heart disease.
The researchers found that eight of the Japanese families had protein-truncating variants in APOB, and that individuals with one of those variants had LDL cholesterol levels 55 milligrams per deciliter lower and triglyceride levels 53 percent lower than those who did not have an APOB variant.
Among the participants of the dozen coronary heart disease studies, the researchers found 56 people with these APOB gene variants, and again found lower LDL cholesterol and triglyceride levels in these participants. Only 0.038 percent of those with coronary heart disease carried an APOB variant, while 0.092 percent of those without coronary heart disease did, indicating that carrying gene variants in APOB reduces the risk of coronary heart disease.
The study’s other co-lead author was Akihiro Nomura of the Kanazawa University Graduate School of Medicine in Kanazawa, Japan. The study’s senior author was Sekar Kathiresan of the Broad Institute and Massachusetts General Hospital.
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