LDLR and atherosclerosis: They are classified as GOF or LOF, depending on their linkage to increased or decreased average blood cholesterol, respectively.119 Several SNPs have been experimentally proven to modify LDLR-degrading activity.16,70 GOF SNPs correlate with CVD risk, while LOF SNPs provide cardiovascular protection.23,120 Nonetheless, a clear connection may not yet be established between blood PCSK9 levels and the severity of subclinical atherosclerosis in patients who show no signs of CVD.121