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. This evidence concerns the gene PCSK9 and atherosclerosis.