APOC3 gene rare mutations were associated with lower triglyceride levels and lower risk for cardiovascular disease in two studies published by The New England Journal of Medicine this week. Rare mutations in the APOC3 gene were shown to be associated with significantly reduced triglyceride levels. Since higher plasma triglyceride levels are associated with higher risk of ischemic cardiovascular disease, and lower triglyceride levels are associated with lower risk of cardiovascular disease, the rare variants of this gene may provide lower risk of coronary problems.
The versions of the APOC3 gene that were shown to be associated with lower triglyceride levels were rare. These rare mutations were aggregated for the analysis, which means they were considered as one group in the analysis. The rare versions of the APOC3 gene disrupt the function of the APOC3 protein and lower the level of the APOC3 protein in the blood. Lower levels of functioning APOC3 protein result in lower triglyceride levels in the blood.
In a previously reported study involving an Amish population, it was shown that people with APOC3 mutations that disrupted the production of APOC3 could drink something like a milkshake and not have their triglyceride levels change. Contrarily, when people with a normal version of the APOC3 gene drink a milkshake, their triglyceride levels spike.
The meaning of the two studies is those with a version of the APOC3 gene that reduce APOC3 levels are genetically “fortunate” in that they have lower triglyceride levels and therefore lower risk for coronary problems. Neither of the studies commented on versions of the APOC3 gene that may be associated with higher triglyceride levels. The analyses in the studies did not produce data that suggested anything about having versions of the APOC3 genes that produce higher APOC3 protein levels and therefore higher risk for coronary problems. This may be considered in further research studies.
One of the studies was carried out at the Copenhagen University Hospital in Denmark. In this study, 75,725 subjects participated in the study. The results from this study showed people with rare versions of the gene that reduced APOC3 levels had a 44 percent reduction in triglyceride levels and a 36 percent lower risk for heart attack. The other study was part of the Exome Sequencing Project and was carried out by researchers at the Broad Institute at the Massachusetts General Hospital. In this study, genetic analysis was carried out on the DNA of almost 4,000 people and triglyceride levels were measured as well.
Pharmaceutical companies may use the results from these studies to consider developing a drug that will lower APOC3 protein levels, which may then lower triglyceride levels and risk for cardiovascular disease. While the research studies provided strong support for considering development of this type of drug, a more complex picture might appear as more information about the APOC3 protein and triglycerides emerges. Discovering the rare mutations in the APOC3 gene that were associated with reduced triglyceride levels and lower cardiovascular risk will provide much fuel for further study of the role of triglycerides and heart disease.
By Margaret Lutze