{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:44:46Z","timestamp":1792518286811,"version":"4.5.0"},"reference-count":28,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5816","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2007,3,2]]},"abstract":"<jats:p>\n                    Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in\n                    <jats:italic>LRP6<\/jats:italic>\n                    , which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor\u2013like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors.\n                  <\/jats:p>","DOI":"10.1126\/science.1136370","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T05:46:06Z","timestamp":1172814366000},"page":"1278-1282","source":"Crossref","is-referenced-by-count":540,"title":["<i>LRP6<\/i>\n                    Mutation in a Family with Early Coronary Disease and Metabolic Risk Factors"],"prefix":"10.1126","volume":"315","author":[{"given":"Arya","family":"Mani","sequence":"first","affiliation":[{"name":"Departments of Internal Medicine, Genetics and Molecular Biophysics, and Biochemistry, Howard Hughes Medical Institute and Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Material Science, Amir Kabir University of Technology, Tehran 15875\/4413, Iran."},{"name":"Department of Human Sciences, Azad University of Tehran, Tehran 13185\/786, Iran."},{"name":"Genetics Research Center, The Social Welfare and Rehabilitation Sciences University, Tehran 19875\/383, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayaram","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Genetics and Molecular Biophysics, and Biochemistry, Howard Hughes Medical Institute and Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Material Science, Amir Kabir University of Technology, Tehran 15875\/4413, Iran."},{"name":"Department of Human Sciences, Azad University of Tehran, Tehran 13185\/786, Iran."},{"name":"Genetics Research Center, The Social Welfare and Rehabilitation Sciences University, Tehran 19875\/383, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Genetics and Molecular Biophysics, and Biochemistry, Howard Hughes Medical Institute and Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Material Science, Amir Kabir University of Technology, Tehran 15875\/4413, Iran."},{"name":"Department of Human Sciences, Azad University of Tehran, Tehran 13185\/786, Iran."},{"name":"Genetics Research Center, The Social Welfare and Rehabilitation Sciences University, Tehran 19875\/383, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaleh","family":"Mani","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Genetics and Molecular Biophysics, and Biochemistry, Howard Hughes Medical Institute 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Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khary S.","family":"Carew","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Genetics and Molecular Biophysics, and Biochemistry, Howard Hughes Medical Institute and Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Material Science, Amir Kabir University of Technology, Tehran 15875\/4413, Iran."},{"name":"Department of Human Sciences, Azad University of Tehran, Tehran 13185\/786, Iran."},{"name":"Genetics Research Center, The Social Welfare and Rehabilitation Sciences University, Tehran 19875\/383, Iran."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrikant","family":"Mane","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine, Genetics and Molecular Biophysics, and Biochemistry, Howard Hughes Medical 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Research supported in part by an NIH KO8 award (to A.M.) and grants P50 HL55007 and P01DK68229 from NIH (to R.L.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1136370","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:07:26Z","timestamp":1704856046000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1136370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3,2]]},"references-count":28,"journal-issue":{"issue":"5816","published-print":{"date-parts":[[2007,3,2]]}},"alternative-id":["10.1126\/science.1136370"],"URL":"https:\/\/doi.org\/10.1126\/science.1136370","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3,2]]}}}