Harnessing the Power of Genetics to Advance Cardiovascular Medicine

Prior work has established that individuals with loss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3), which produces a protein that inhibits lipoprotein lipase, have reduced levels of plasma triglycerides, LDL-cholesterol, and HDL-cholesterol. The association of these variants with cardiovascular risk is as yet undetermined.

In a manufacturer-sponsored study (ClinicalTrials.gov NCT01749878), investigators examined DNA samples from 58,335 adults of European ancestry and identified 13 distinct loss-of-function variants in ANGPTL3 in 246 individuals. Compared with noncarriers, carriers of loss-of-function variants had lower levels of triglycerides (−27%), LDL (−9%), and HDL (−4%). In a case-control study adjusted for age, sex, a…