{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:06:42Z","timestamp":1792426002013,"version":"4.5.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,7,19]],"date-time":"2013-07-19T00:00:00Z","timestamp":1374192000000},"content-version":"vor","delay-in-days":2697,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2006,3]]},"DOI":"10.1086\/500615","type":"journal-article","created":{"date-parts":[[2006,2,3]],"date-time":"2006-02-03T15:06:45Z","timestamp":1138979205000},"page":"410-422","source":"Crossref","is-referenced-by-count":473,"title":["A Spectrum of PCSK9 Alleles Contributes to Plasma Levels of Low-Density Lipoprotein Cholesterol"],"prefix":"10.1016","volume":"78","author":[{"given":"Ingrid K.","family":"Kotowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Pertsemlidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Luke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria L.","family":"Vega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen H.","family":"Hobbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1086\/500615_bib6","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":"10.1086\/500615_bib7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","article-title":"Haploview: analysis and visualization of LD and haplotype maps","volume":"21","author":"Barrett","year":"2005","journal-title":"Bioinformatics"},{"key":"10.1086\/500615_bib8","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 LDLR and LDL-cholesterol","volume":"279","author":"Benjannet","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1086\/500615_bib9","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1101\/gr.789803","article-title":"AVID: a global alignment program","volume":"13","author":"Bray","year":"2003","journal-title":"Genome Res"},{"key":"10.1086\/500615_bib10","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/hep.20466","article-title":"Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity","volume":"40","author":"Browning","year":"2004","journal-title":"Hepatology"},{"key":"10.1086\/500615_bib11","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":"10.1086\/500615_bib12","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":"10.1086\/500615_bib13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1101\/gr.762503","article-title":"Strategies and tools for whole-genome alignments","volume":"13","author":"Couronne","year":"2003","journal-title":"Genome Res"},{"key":"10.1086\/500615_bib14","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":"10.1086\/500615_bib15","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1126\/science.1069424","article-title":"The structure of haplotype blocks in the human genome","volume":"296","author":"Gabriel","year":"2002","journal-title":"Science"},{"key":"10.1086\/500615_bib16","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":"10.1086\/500615_bib17","first-page":"2863","article-title":"Familial hypercholesterolemia","volume":"Vol II","author":"Goldstein","year":"2001"},{"key":"10.1086\/500615_bib18","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1056\/NEJM199304223281603","article-title":"Genetic and environmental influences on serum lipid levels in twins","volume":"328","author":"Heller","year":"1993","journal-title":"N Engl J Med"},{"key":"10.1086\/500615_bib19","doi-asserted-by":"crossref","first-page":"12027","DOI":"10.1073\/pnas.1534923100","article-title":"Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes","volume":"100","author":"Horton","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1086\/500615_bib20","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1016\/S0022-2275(20)42605-7","article-title":"Familial defective apolipoprotein B-100: a mutation of apolipoprotein B that causes hypercholesterolemia","volume":"31","author":"Innerarity","year":"1990","journal-title":"J Lipid Res"},{"key":"10.1086\/500615_bib21","doi-asserted-by":"crossref","first-page":"14878","DOI":"10.1073\/pnas.232565499","article-title":"DobzhanskyMuller incompatibilities in protein evolution","volume":"99","author":"Kondrashov","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1086\/500615_bib22","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1194\/jlr.M400396-JLR200","article-title":"Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells","volume":"46","author":"Lalanne","year":"2005","journal-title":"J Lipid Res"},{"key":"10.1086\/500615_bib23","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":"10.1086\/500615_bib24","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":"10.1086\/500615_bib25","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":"10.1086\/500615_bib26","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":"10.1086\/500615_bib27","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: predicting amino acid changes that affect protein function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"10.1086\/500615_bib28","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":"10.1086\/500615_bib29","doi-asserted-by":"crossref","first-page":"50630","DOI":"10.1074\/jbc.M410077200","article-title":"Post-transcriptional regulation of LDL receptor protein by proprotein convertase subtilisin\/kexin type 9a (PCSK9) in mouse liver","volume":"279","author":"Park","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1086\/500615_bib30","first-page":"888","article-title":"The Cincinnati Lipid Research Clinic family study: cultural and biological determinants of lipids and lipoprotein concentrations","volume":"34","author":"Rao","year":"1982","journal-title":"Am J Hum Genet"},{"key":"10.1086\/500615_bib31","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"},{"issue":"Suppl 9B","key":"10.1086\/500615_bib32","doi-asserted-by":"crossref","first-page":"13S","DOI":"10.1016\/S0002-9343(01)00987-1","article-title":"Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease","volume":"113","author":"Sacks","year":"2002","journal-title":"Am J Med"},{"key":"10.1086\/500615_bib33","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1194\/jlr.M200342-JLR200","article-title":"Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis","volume":"44","author":"Schonfeld","year":"2003","journal-title":"J Lipid Res"},{"key":"10.1086\/500615_bib34","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":"PNAS"},{"key":"10.1086\/500615_bib35","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":"10.1086\/500615_bib36","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":"10.1086\/500615_bib37","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/hmg\/10.6.591","article-title":"Prediction of deleterious human alleles","volume":"10","author":"Sunyaev","year":"2001","journal-title":"Hum Mol Genet"},{"key":"10.1086\/500615_bib38","doi-asserted-by":"crossref","first-page":"E462","DOI":"10.1152\/ajpendo.00064.2004","article-title":"Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population","volume":"288","author":"Szczepaniak","year":"2004","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"10.1086\/500615_bib39","series-title":"R: a language and environment for statistical computing","author":"The R Development Core Team","year":"2004"},{"key":"10.1086\/500615_bib40","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1093\/nar\/gkg115","article-title":"PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification","volume":"31","author":"Thomas","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"10.1086\/500615_bib41","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":"10.1086\/500615_bib42","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"}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929707623817?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929707623817?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T12:52:34Z","timestamp":1627044754000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929707623817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,3]]}},"alternative-id":["S0002929707623817"],"URL":"https:\/\/doi.org\/10.1086\/500615","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2006,3]]}}}