A rare mutation discovered at Amgen subsidiary deCODE Genetics is associated with a 34 percent lower risk of coronary artery disease. Amgen scientists aim to turn this insight into a new type of heart drug, which might complement lipid-lowering drugs by addressing other potential risk factors for heart disease.
While cholesterol levels are strongly linked to the risk for heart disease, it also appears that cholesterol by itself doesn’t tell the whole story. There are people with high levels of bad cholesterol who never develop heart disease, and people with lower-than-average cholesterol levels can still suffer heart attacks. This suggests that blood lipids are not the sole risk factor for heart disease, and that other factors may also contribute to atherosclerosis. Identifying these other contributing biological pathways could lead to entirely new types of cardiovascular drugs.
In a study based on genome, cholesterol, and heart disease data from 700,000 people in seven countries, researchers found that a rare mutation in a gene called ASGR1 reduced the risk for coronary artery disease by 34 percent.1 The mutation also decreased non-HDL cholesterol (total cholesterol minus good cholesterol) by 15.3 milligrams per deciliter, or roughly 10 percent. While this decline is significant, the mutation appears to confer greater protection against coronary heart disease than can easily be accounted for by the reduction in cholesterol alone.1,2 This suggests the mutation affects another yet to be identified risk factor.