{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:49:39Z","timestamp":1791352179360,"version":"4.3.1"},"reference-count":87,"publisher":"Hindawi Limited","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2401,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"R\u00e9gion \u00cele-de-France, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, GIS-Institut des Maladies Rares"},{"name":"Agence Nationale de la Recherche (ANR) \u201cCardiovascular, Obesity, and Diabetes 2005\u201d"},{"name":"ANR-Maladies Rares 2006"},{"name":"Universit\u00e9 Ren\u00e9 Descartes"},{"name":"Conseil de la Recherche de l'Universit\u00e9 Saint-Joseph and Franco-Lebanese Program (CEDRE)"},{"name":"AQ2PHRC Assistance Publique-H\u00f4pitaux de Paris (AP-HP)","award":["AOM06024"],"award-info":[{"award-number":["AOM06024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hum. Mutat."],"published-print":{"date-parts":[[2009,4]]},"DOI":"10.1002\/humu.20882","type":"journal-article","created":{"date-parts":[[2009,2,4]],"date-time":"2009-02-04T00:24:14Z","timestamp":1233707054000},"page":"520-529","source":"Crossref","is-referenced-by-count":224,"title":["Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (<i>PCSK9<\/i>) gene in cholesterol metabolism and disease"],"prefix":"10.1155","volume":"30","author":[{"given":"Marianne","family":"Abifadel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Rab\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Devillers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold","family":"Munnich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00e8le","family":"Erlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Junien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Varret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Boileau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"98","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"10.1002\/humu.20882-BIB1|cit1","doi-asserted-by":"crossref","first-page":"e1043","DOI":"10.1371\/journal.pone.0001043","article-title":"Proprotein convertase subtilisin\/kexin type 9 (PCSK9) gene is a risk factor of large-vessel atherosclerosis stroke","volume":"2","author":"Abboud","year":"2007","journal-title":"PLoS ONE"},{"key":"10.1002\/humu.20882-BIB2|cit2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/ng1161","article-title":"Mutations in PCSK9 cause autosomal dominant hypercholesterolemia","volume":"34","author":"Abifadel","year":"2003","journal-title":"Nat Genet"},{"key":"10.1002\/humu.20882-BIB3|cit3","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1051\/medsci\/20062211916","article-title":"PCSK9, from gene to protein: a new actor involved in cholesterol homeostasis","volume":"22","author":"Abifadel","year":"2006","journal-title":"Med Sci (Paris)"},{"key":"10.1002\/humu.20882-BIB4|cit4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ando.2007.02.002","article-title":"After the LDL receptor and apolipoprotein B, autosomal dominant hypercholesterolemia reveals its third protagonist: PCSK9","volume":"68","author":"Abifadel","year":"2007","journal-title":"Ann Endocrinol (Paris)"},{"key":"10.1002\/humu.20882-BIB5|cit5","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1373\/clinchem.2007.091280","article-title":"Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum ldl cholesterol","volume":"53","author":"Alborn","year":"2007","journal-title":"Clin Chem"},{"key":"10.1002\/humu.20882-BIB6|cit6","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/humu.9383","article-title":"Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia","volume":"26","author":"Allard","year":"2005","journal-title":"Hum Mutat"},{"key":"10.1002\/humu.20882-BIB7|cit7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/oxfordjournals.aje.a114531","article-title":"Risk factors for coronary heart disease in adult female twins. Genetic heritability and shared environmental influences","volume":"125","author":"Austin","year":"1987","journal-title":"Am J Epidemiol"},{"key":"10.1002\/humu.20882-BIB8|cit8","doi-asserted-by":"crossref","first-page":"48865","DOI":"10.1074\/jbc.M409699200","article-title":"NARC-1\/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol","volume":"279","author":"Benjannet","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.20882-BIB9|cit9","doi-asserted-by":"crossref","first-page":"30561","DOI":"10.1074\/jbc.M606495200","article-title":"The proprotein convertase (PC) PCSK9 is inactivated by furin and\/or PC5\/6A: functional consequences of natural mutations and post-translational modifications","volume":"281","author":"Benjannet","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.20882-BIB10|cit10","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1161\/01.ATV.0000204337.81286.1c","article-title":"Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy","volume":"26","author":"Berge","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1002\/humu.20882-BIB11|cit11","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.atherosclerosis.2007.07.019","article-title":"On behalf of the investigators of the Portuguese FH study. Familial hypercholesterolaemia in Portugal","volume":"196","author":"Bourbon","year":"2007","journal-title":"Atherosclerosis"},{"key":"10.1002\/humu.20882-BIB12|cit12","doi-asserted-by":"crossref","first-page":"11041","DOI":"10.1073\/pnas.96.20.11041","article-title":"A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood","volume":"96","author":"Brown","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/humu.20882-BIB13|cit13","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1126\/science.1125884","article-title":"Biomedicine. Lowering LDL-not only how low, but how long?","volume":"311","author":"Brown","year":"2006","journal-title":"Science"},{"key":"10.1002\/humu.20882-BIB14|cit14","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1093\/hmg\/ddl077","article-title":"Effect of mutations in the PCSK9 gene on the cell surface LDL receptors","volume":"15","author":"Cameron","year":"2006","journal-title":"Hum Mol Genet"},{"key":"10.1002\/humu.20882-BIB15|cit15","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1365-2796.2007.01915.x","article-title":"Characterization of novel mutations in the catalytic domain of the PCSK9 gene","volume":"263","author":"Cameron","year":"2008","journal-title":"J Intern Med"},{"key":"10.1002\/humu.20882-BIB16|cit16","article-title":"Berberine decreases PCSK9 expression in HepG2 cells","author":"Cameron","journal-title":"Atherosclerosis"},{"key":"10.1002\/humu.20882-BIB17|cit17","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1194\/jlr.M700437-JLR200","article-title":"Atorvastatin increases human serum levels of proprotein convertase subtilisin kexin type 9 (PCSK9)","volume":"49","author":"Careskey","year":"2008","journal-title":"J Lipid Res"},{"key":"10.1002\/humu.20882-BIB18|cit18","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.jacc.2005.01.051","article-title":"A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis","volume":"45","author":"Chen","year":"2005","journal-title":"J Am Coll Cardiol"},{"key":"10.1002\/humu.20882-BIB19|cit19","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/ng1509","article-title":"Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9","volume":"37","author":"Cohen","year":"2005","journal-title":"Nat Genet"},{"key":"10.1002\/humu.20882-BIB20|cit20","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1056\/NEJMoa054013","article-title":"Sequence variations in PCSK9, low LDL, and protection against coronary heart disease","volume":"354","author":"Cohen","year":"2006","journal-title":"N Engl J Med"},{"key":"10.1002\/humu.20882-BIB21|cit21","doi-asserted-by":"crossref","first-page":"6211","DOI":"10.1074\/jbc.M508582200","article-title":"Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c","volume":"281","author":"Costet","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.20882-BIB22|cit22","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nsmb1235","article-title":"Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia","volume":"14","author":"Cunningham","year":"2007","journal-title":"Nat Struct Mol Biol"},{"key":"10.1002\/humu.20882-BIB23|cit23","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1111\/j.1742-4658.2008.06495.x","article-title":"PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans","volume":"275","author":"Dewpura","year":"2008","journal-title":"FEBS J"},{"key":"10.1002\/humu.20882-BIB24|cit24","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1161\/01.ATV.0000134621.14315.43","article-title":"Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia","volume":"24","author":"Dubuc","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1002\/humu.20882-BIB25|cit25","doi-asserted-by":"crossref","first-page":"11265","DOI":"10.1074\/jbc.M109011200","article-title":"Biosynthesis and cellular trafficking of the convertase SKI-1\/S1P: ectodomain shedding requires SKI-1 activity","volume":"277","author":"Elagoz","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.20882-BIB26|cit26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/1471-2350-7-66","article-title":"The E670G SNP in the PCSK9 gene is associated with polygenic hypercholesterolemia in men but not in women","volume":"7","author":"Evans","year":"2006","journal-title":"BMC Med Genet"},{"key":"10.1002\/humu.20882-BIB27|cit27","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1021\/bi7016359","article-title":"Self-association of human PCSK9 correlates with its LDLR-degrading activity","volume":"47","author":"Fan","year":"2008","journal-title":"Biochemistry"},{"key":"10.1002\/humu.20882-BIB28|cit28","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/01.ATV.0000255311.26383.2f","article-title":"A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol","volume":"27","author":"Fasano","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1002\/humu.20882-BIB29|cit29","doi-asserted-by":"crossref","first-page":"20502","DOI":"10.1074\/jbc.M701634200","article-title":"Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation","volume":"282","author":"Fisher","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.20882-BIB30|cit30","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1158\/1055-9965.EPI-07-0502","article-title":"Sequence variation in proprotein convertase subtilisin\/kexin type 9 serine protease gene, low LDL cholesterol, and cancer incidence","volume":"16","author":"Folsom","year":"2007","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"10.1002\/humu.20882-BIB31|cit31","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1056\/NEJM196702022760507","article-title":"Fat transport in lipoproteins-an integrated approach to mechanisms and disorders","volume":"276","author":"Fredrickson","year":"1967","journal-title":"N Engl J Med"},{"key":"10.1002\/humu.20882-BIB32|cit32","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1126\/science.1060458","article-title":"Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein","volume":"292","author":"Garcia","year":"2001","journal-title":"Science"},{"key":"10.1002\/humu.20882-BIB33|cit33","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1172\/JCI107332","article-title":"Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia","volume":"52","author":"Goldstein","year":"1973","journal-title":"J Clin Invest"},{"key":"10.1002\/humu.20882-BIB34|cit34","first-page":"8","article-title":"Familial hypercholesterolemia: pathogenesis of a receptor disease","volume":"143","author":"Goldstein","year":"1978","journal-title":"Johns Hopkins Med J"},{"key":"10.1002\/humu.20882-BIB35|cit35","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1194\/jlr.C600025-JLR200","article-title":"Antisense inhibition of proprotein convertase subtilisin\/kexin type 9 reduces serum LDL in hyperlipidemic mice","volume":"48","author":"Graham","year":"2007","journal-title":"J Lipid Res"},{"key":"10.1002\/humu.20882-BIB36|cit36","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1194\/jlr.M800027-JLR200","article-title":"Plasma PCSK9 preferentially reduces liver LDL receptors in mice","volume":"49","author":"Grefhorst","year":"2008","journal-title":"J Lipid Res"},{"key":"10.1002\/humu.20882-BIB37|cit37","doi-asserted-by":"crossref","first-page":"14604","DOI":"10.1073\/pnas.0703402104","article-title":"The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain","volume":"104","author":"Hampton","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/humu.20882-BIB38|cit38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1471-2121-8-9","article-title":"Degradation of the LDL receptors by PCSK9 is not mediated by a secreted protein acted upon by PCSK9 extracellularly","volume":"8","author":"Holla","year":"2007","journal-title":"BMC Cell Biol"},{"key":"10.1002\/humu.20882-BIB39|cit39","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.atherosclerosis.2007.07.022","article-title":"Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa","volume":"196","author":"Homer","year":"2007","journal-title":"Atherosclerosis"},{"key":"10.1002\/humu.20882-BIB40|cit40","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.atherosclerosis.2006.08.039","article-title":"The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population","volume":"193","author":"Hooper","year":"2007","journal-title":"Atherosclerosis"},{"key":"10.1002\/humu.20882-BIB41|cit41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.tibs.2006.12.008","article-title":"Molecular biology of PCSK9: its role in LDL metabolism","volume":"32","author":"Horton","year":"2007","journal-title":"Trends Biochem Sci"},{"key":"10.1002\/humu.20882-BIB42|cit42","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1161\/01.ATV.20.4.1089","article-title":"Genetic localization to chromosome 1p32 of the third locus for familial hypercholesterolemia in a Utah kindred","volume":"20","author":"Hunt","year":"2000","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1002\/humu.20882-BIB43|cit43","doi-asserted-by":"crossref","first-page":"6919","DOI":"10.1073\/pnas.84.19.6919","article-title":"Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding","volume":"84","author":"Innerarity","year":"1987","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/humu.20882-BIB44|cit44","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1056\/NEJMc0707445","article-title":"A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction","volume":"358","author":"Kathiresan","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1002\/humu.20882-BIB45|cit45","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/0002-9343(64)90196-2","article-title":"The inheritance of essential familial hypercholesterolemia","volume":"37","author":"Khachadurian","year":"1964","journal-title":"Am J Med"},{"key":"10.1002\/humu.20882-BIB46|cit46","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1086\/500615","article-title":"A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol","volume":"78","author":"Kotowski","year":"2006","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.20882-BIB47|cit47","doi-asserted-by":"crossref","first-page":"9666","DOI":"10.1074\/jbc.M705831200","article-title":"Dual mechanisms for the fibrate-mediated repression of proprotein convertase subtilisin\/kexin type 9","volume":"283","author":"Kourimate","year":"2008","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.20882-BIB48|cit48","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1073\/pnas.0712064105","article-title":"Molecular basis for LDL receptor recognition by PCSK9","volume":"105","author":"Kwon","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/humu.20882-BIB49|cit49","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1172\/JCI29383","article-title":"Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice","volume":"116","author":"Lagace","year":"2006","journal-title":"J Clin Invest"},{"key":"10.1002\/humu.20882-BIB50|cit50","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1210\/en.2006-0098","article-title":"Fasting induces hyperlipidemia in mice overexpressing proprotein convertase subtilisin kexin type 9: lack of modulation of very-low-density lipoprotein hepatic output by the low-density lipoprotein receptor","volume":"147","author":"Lambert","year":"2006","journal-title":"Endocrinology"},{"key":"10.1002\/humu.20882-BIB51|cit51","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1373\/clinchem.2007.099747","article-title":"Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment","volume":"54","author":"Lambert","year":"2008","journal-title":"Clin Chem"},{"key":"10.1002\/humu.20882-BIB52|cit52","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.febslet.2008.02.038","article-title":"Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes","volume":"582","author":"Langhi","year":"2008","journal-title":"FEBS Lett"},{"key":"10.1002\/humu.20882-BIB53|cit53","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/j.0009-9163.2004.0238.x","article-title":"Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia","volume":"65","author":"Leren","year":"2004","journal-title":"Clin Genet"},{"key":"10.1002\/humu.20882-BIB54|cit54","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1042\/BJ20070664","article-title":"Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity","volume":"406","author":"Li","year":"2007","journal-title":"Biochem J"},{"key":"10.1002\/humu.20882-BIB55|cit55","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/35025203","article-title":"Atherosclerosis","volume":"407","author":"Lusis","year":"2000","journal-title":"Nature"},{"key":"10.1002\/humu.20882-BIB56|cit56","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1194\/jlr.M300203-JLR200","article-title":"Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice","volume":"44","author":"Maxwell","year":"2003","journal-title":"J Lipid Res"},{"key":"10.1002\/humu.20882-BIB57|cit57","doi-asserted-by":"crossref","first-page":"7100","DOI":"10.1073\/pnas.0402133101","article-title":"Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype","volume":"101","author":"Maxwell","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/humu.20882-BIB58|cit58","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1073\/pnas.0409736102","article-title":"Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment","volume":"102","author":"Maxwell","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/humu.20882-BIB59|cit59","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.bbrc.2007.07.029","article-title":"Plasma PCSK9 levels correlate with cholesterol in men but not in women","volume":"361","author":"Mayne","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1002\/humu.20882-BIB60|cit60","first-page":"7","article-title":"Plasma PCSK9 levels are significantly modified by statins and fibrates in humans","volume":"11","author":"Mayne","year":"2008","journal-title":"Lipids Health Dis"},{"key":"10.1002\/humu.20882-BIB61|cit61","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.mehy.2007.03.018","article-title":"Of PCSK9, cholesterol homeostasis and parasitic infections: Possible survival benefits of loss-of-function PCSK9 genetic polymorphisms","volume":"69","author":"Mbikay","year":"2007","journal-title":"Med Hypotheses"},{"key":"10.1002\/humu.20882-BIB62|cit62","doi-asserted-by":"crossref","first-page":"20799","DOI":"10.1074\/jbc.C700095200","article-title":"Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells","volume":"282","author":"McNutt","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.20882-BIB63|cit63","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.atherosclerosis.2006.12.035","article-title":"Genetic variants in PCSK9 in the Japanese population: Rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population","volume":"196","author":"Miyake","year":"2008","journal-title":"Atherosclerosis"},{"key":"10.1002\/humu.20882-BIB64|cit64","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/S0022-3476(74)80506-8","article-title":"Pseudohomozygous type II hyperlipoproteinemia","volume":"85","author":"Morganroth","year":"1974","journal-title":"J Pediatr"},{"key":"10.1002\/humu.20882-BIB65|cit65","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1161\/01.ATV.0000190668.94752.ab","article-title":"Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response","volume":"25","author":"Naoumova","year":"2005","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1002\/humu.20882-BIB66|cit66","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/j.1600-0854.2007.00562.x","article-title":"The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR","volume":"8","author":"Nassoury","year":"2007","journal-title":"Traffic"},{"key":"10.1002\/humu.20882-BIB67|cit67","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.abb.2003.09.011","article-title":"Functional characterization of Narc 1, a novel proteinase related to proteinase K","volume":"420","author":"Naureckiene","year":"2003","journal-title":"Arch Biochem Biophys"},{"key":"10.1002\/humu.20882-BIB68|cit68","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1161\/01.ATV.0000133684.77013.88","article-title":"Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related to mutations in PCSK9","volume":"24","author":"Ouguerram","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1002\/humu.20882-BIB69|cit69","doi-asserted-by":"crossref","first-page":"50630","DOI":"10.1074\/jbc.M410077200","article-title":"Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin\/kexin type 9a in mouse liver","volume":"279","author":"Park","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.20882-BIB70|cit70","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.str.2007.04.004","article-title":"The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol","volume":"15","author":"Piper","year":"2007","journal-title":"Structure"},{"key":"10.1002\/humu.20882-BIB71|cit71","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.atherosclerosis.2005.08.015","article-title":"Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia","volume":"186","author":"Pisciotta","year":"2006","journal-title":"Atherosclerosis"},{"key":"10.1002\/humu.20882-BIB72|cit72","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1111\/j.1471-4159.2006.03928.x","article-title":"Implication of the proprotein convertase NARC-1\/PCSK9 in the development of the nervous system","volume":"98","author":"Poirier","year":"2006","journal-title":"J Neurochem"},{"key":"10.1002\/humu.20882-BIB73|cit73","doi-asserted-by":"crossref","first-page":"5374","DOI":"10.1073\/pnas.0501652102","article-title":"Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9","volume":"102","author":"Rashid","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/humu.20882-BIB74|cit74","first-page":"419","article-title":"Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study","volume":"63","author":"Rice","year":"1991","journal-title":"Hum Biol"},{"key":"10.1002\/humu.20882-BIB75|cit75","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/sj.ejhg.5200516","article-title":"Autosomal dominant type IIa hypercholesterolemia: evaluation of the respective contributions of LDLR and APOB genes defects as well as a third major group of defects","volume":"8","author":"Saint-Jore","year":"2000","journal-title":"Eur J Hum Genet"},{"key":"10.1002\/humu.20882-BIB76|cit76","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1042\/CS20070150","article-title":"The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U","volume":"113","author":"Scartezini","year":"2007","journal-title":"K. men. Clin Sci (Lond)"},{"key":"10.1002\/humu.20882-BIB77|cit77","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.bbrc.2008.04.004","article-title":"Secreted proprotein convertase subtilisin\/kexin type 9 reduces both hepatic and extrahepatic low-density lipoprotein receptors in vivo","volume":"1370","author":"Schmidt","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1002\/humu.20882-BIB78|cit78","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1042\/bse0380079","article-title":"Precursor convertases in the secretory pathway, cytosol and extracellular milieu","volume":"38","author":"Seidah","year":"2002","journal-title":"Essays Biochem"},{"key":"10.1002\/humu.20882-BIB79|cit79","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1073\/pnas.0335507100","article-title":"The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation","volume":"100","author":"Seidah","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/humu.20882-BIB80|cit80","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s10038-003-0114-3","article-title":"Genetic variants in PCSK9 affect the cholesterol level in Japanese","volume":"49","author":"Shioji","year":"2004","journal-title":"J Hum Genet"},{"key":"10.1002\/humu.20882-BIB81|cit81","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1093\/hmg\/ddi128","article-title":"Evidence for effect of mutant PCSK9 on apolipoprotein B secretion as the cause of unusually severe dominant hypercholesterolaemia","volume":"14","author":"Sun","year":"2005","journal-title":"Hum Mol Genet"},{"key":"10.1002\/humu.20882-BIB82|cit82","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00439-003-1071-9","article-title":"A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree","volume":"114","author":"Timms","year":"2004","journal-title":"Hum Genet"},{"key":"10.1002\/humu.20882-BIB83|cit83","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1086\/302370","article-title":"A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32","volume":"64","author":"Varret","year":"1999","journal-title":"Am J Hum Genet"},{"key":"10.1002\/humu.20882-BIB84|cit84","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.amjcard.2004.02.058","article-title":"The Dallas Heart Study: a population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health","volume":"93","author":"Victor","year":"2004","journal-title":"Am J Cardiol"},{"key":"10.1002\/humu.20882-BIB85|cit85","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/humu.20316","article-title":"The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL-cholesterol in a Caucasian population","volume":"27","author":"Yue","year":"2006","journal-title":"Hum Mutat"},{"key":"10.1002\/humu.20882-BIB86|cit86","doi-asserted-by":"crossref","first-page":"18602","DOI":"10.1074\/jbc.M702027200","article-title":"Binding of proprotein convertase subtilisin\/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation","volume":"282","author":"Zhang","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1002\/humu.20882-BIB87|cit87","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1086\/507488","article-title":"Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote","volume":"79","author":"Zhao","year":"2006","journal-title":"Am J Hum Genet"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhumu.20882","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1002\/humu.20882","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T16:52:34Z","timestamp":1672332754000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/humu.20882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,3]]},"references-count":87,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,4]]}},"URL":"https:\/\/doi.org\/10.1002\/humu.20882","archive":["Portico"],"relation":{},"ISSN":["1059-7794"],"issn-type":[{"value":"1059-7794","type":"print"}],"subject":[],"published":{"date-parts":[[2009,2,3]]}}}