Located on chromosome 1, the PCSK9 gene provides instructions for making a protein that helps regulate the amount of cholesterol in the bloodstream. Several PCSK9 mutations are known that cause an inherited form of high cholesterol (familial hypercholesterolemia). Other mutations in the PCSK9 gene result in reduced blood cholesterol levels (hypocholesterolemia).GHR
Widespread DNA-based population screening of the PCSK9 gene as well as two other genes (LDLR and APOB) for familial hypercholesterolemia mutations is under discussion in several countries; one such discussion was published by the CDC in 2019 here as well as here.
Clinically, PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors have emerged as a class of low-density lipoprotein cholesterol (LDL-C)–lowering drugs that lower LDL-C by approximately 60% and may thereby reduce the risk of major vascular events. In 2019, one report was published that suggested that a polygenic risk score based on 27 SNPs (GRS-27) might distinguish between patients who, regardless of clinical risk factors, gained benefit from taking evolocumab (a PCSK9 inhibitor) versus those who wouldn't.[PMID 31707849]