Mutations in PCSK9 cause autosomal dominant hypercholesterolemia

By M. Abifadel, M. Varret, J. Rabès, D. Allard, K. Ouguerram, M. Devillers, C. Cruaud, S. Benjannet, L. Wickham, D. Erlich and 16 more. Nature Genetics, 2003

2,961 citations recorded by the source corpus.

Subfields: Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/80bf33c74bfe780bcc1968f318b09647e59f0afe

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Citations in the corpus

Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease (2018, methodology): “p1); (2) the Exome Sequencing Project Early-Onset Myocardial Infarction (ESP-EOMI) study(9); (3) a nested case-control cohort from the Jackson Heart Study (JHS); (4) the South German Myocardial Infarction study (dbGaP Study Accession phs000916.”
Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates (2008, background): “PCSK9 was the first family member to be implicated in a dominantly inherited form of hypercholesterolemia (3).”
European guidelines on cardiovascular disease prevention in clinical practice: executive summary. (2007, positive): “199 These mutations could cause increased degradation of LDL receptors, reduced numbers of receptors on the surface of the cell, and monogenic hypercholesterolaemia.”
European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invit (2007, positive): “Recently, defects in a third gene called protein convertase subtilisin/kexin type 9 (PCSK9), causing monogenic hypercholesterolaemia, have been identified.(199) These mutations could cause increased degradation of LDL receptors, reduced numbers of receptors on the surface of the cell, and monogenic ”
In vivo genome editing using Staphylococcus aureus Cas9 (2015, background): “Inhibitors of the human convertase PCSK9 have emerged as a promising new class of cardioprotective drugs after human genetic studies revealed that loss of PCSK9 is associated with a reduced risk of cardiovascular disease and lower levels of LDL cholesterol 39–41 .”
A Century of Cholesterol and Coronaries: From Plaques to Genes to Statins (2015, neutral): “The relation between PCSK9 and LDL receptors was discovered by Abifadel et al. (2003) in studies of rare patients with gain-of-function mutations that increase the activity of the protein.”
PCSK9: a convertase that coordinates LDL catabolism Published, JLR Papers in Press, November 19, 2008. (2009, background): “(1) identified three families with autosomal dominant hypercholesterolemia and premature CHD caused by missense mutations in the ninth member of the proprotein convertase family, PCSK9.”
2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. (2019, background): “Recently, a new class of drugs, PCSK9 inhibitors, has become available that targets a protein (PCSK9) involved in the control of the LDLR.(280) Elevated concentration or function of this protein in plasma reduces LDLR expression by promoting, upon binding, LDLR lysosomal catabolism and a subsequent ”
Molecular biology of PCSK9: its role in LDL metabolism. (2007, background): “Another gain-of-function mutation (F216L) is predicted to reside very close to D374Y on the outer surface of the catalytic domain [24] and might also be a Class 5 mutation.”