{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:20:00Z","timestamp":1791930000964,"version":"4.3.4"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              Autosomal dominant hypercholesterolemia (ADH) is due to deleterious variants in\n              <jats:italic>LDLR<\/jats:italic>\n              ,\n              <jats:italic>APOB<\/jats:italic>\n              , or\n              <jats:italic>PCSK9<\/jats:italic>\n              genes. Double heterozygote for these genes induces a more severe phenotype. More recently, a new causative variant of heterozygous ADH was identified in\n              <jats:italic>APOE<\/jats:italic>\n              . Here we study the phenotype of 21 adult patients, double heterozygotes for rare\n              <jats:italic>LDLR<\/jats:italic>\n              and rare\n              <jats:italic>APOE<\/jats:italic>\n              variants (\n              <jats:italic>LDLR+APOE<\/jats:italic>\n              ) in a national wide French cohort.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              <jats:italic>LDLR<\/jats:italic>\n              ,\n              <jats:italic>APOB<\/jats:italic>\n              ,\n              <jats:italic>PCSK9<\/jats:italic>\n              , and\n              <jats:italic>APOE<\/jats:italic>\n              genes were sequenced in 5743 probands addressed for ADH genotyping. The lipid profile and occurrence of premature atherosclerotic cardiovascular diseases were compared between the\n              <jats:italic>LDLR+APOE<\/jats:italic>\n              carriers (n=21) and the carriers of the same\n              <jats:italic>LDLR<\/jats:italic>\n              causative variants alone (n=22).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              The prevalence of\n              <jats:italic>LDLR+APOE<\/jats:italic>\n              carriers in this French ADH cohort is 0.4%. Overall, LDL (low-density lipoprotein)-cholesterol concentrations were 23% higher in\n              <jats:italic>LDLR+APOE<\/jats:italic>\n              patients than in\n              <jats:italic>LDLR<\/jats:italic>\n              patients (9.14\u00b12.51 versus 7.43\u00b11.59 mmol\/L,\n              <jats:italic>P=0<\/jats:italic>\n              .0221). When only deleterious or probably deleterious variants were considered, the LDL-cholesterol concentrations were 46% higher in\n              <jats:italic>LDLR+APOE<\/jats:italic>\n              carriers than in\n              <jats:italic>LDLR<\/jats:italic>\n              carriers (10.83\u00b13.45 versus 7.43\u00b11.59 mmol\/L,\n              <jats:italic>P=0<\/jats:italic>\n              .0270). Two patients exhibited a homozygous familial hypercholesterolemia phenotype (LDL-cholesterol &gt;13 mmol\/L). Premature atherosclerotic cardiovascular disease was more common in\n              <jats:italic>LDLR+APOE<\/jats:italic>\n              patients than in\n              <jats:italic>LDLR<\/jats:italic>\n              carriers (70% versus 30%,\n              <jats:italic>P=0<\/jats:italic>\n              .026).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Although an incomplete penetrance should be taken into account for\n              <jats:italic>APOE<\/jats:italic>\n              variant classification, these results suggest an additive effect of deleterious\n              <jats:italic>APOE<\/jats:italic>\n              variants on ADH phenotype highlighting the relevance of\n              <jats:italic>APOE<\/jats:italic>\n              sequencing.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.319146","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T09:02:00Z","timestamp":1682586120000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Additive Effect of\n            <i>APOE<\/i>\n            Rare Variants on the Phenotype of Familial Hypercholesterolemia"],"prefix":"10.1161","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4916-6613","authenticated-orcid":true,"given":"Oriane","family":"Marmontel","sequence":"first","affiliation":[{"name":"Service de Biochimie et Biologie mol\u00e9culaire, Laboratoire de Biologie M\u00e9dicale Multi-Sites (O.M., E.D., M.D.F.)"},{"name":"Hospices Civils de Lyon, France. CarMen Laboratory, INSERM, INRA, INSA Lyon, Universit\u00e9 Claude Bernard Lyon 1, Pierre-B\u00e9nite, France (O.M., S.C., P.M., N.P., M.D.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3361-3570","authenticated-orcid":true,"given":"Yara","family":"Abou-Khalil","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 Sorbonne Paris Nord, INSERM, LVTS, Paris, France (Y.A.-K., J.-P.R., M.V.)."},{"name":"Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy, P\u00f4le Technologie- Sant\u00e9 (PTS), Saint-Joseph University, Beirut, Lebanon (Y.A.-K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Bluteau","sequence":"additional","affiliation":[{"name":"INSERM UMRS 1166 - ICAN, Faculty of Medicine Pitie-Salp\u00e9tri\u00e8re, Sorbonne University, Paris, France (O.B., A.C.)."},{"name":"Service de Biochimie Endocrinienne et Oncologique, Assistance publique \u2013 H\u00f4pitaux de Paris Sorbonne Universit\u00e9 Piti\u00e9 Salp\u00eatri\u00e8re, Paris, France (O.B., A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-8040","authenticated-orcid":true,"given":"Bertrand","family":"Cariou","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Centre Hospitalier Universitaire NANTES, CNRS, INSERM, l\u2019institut du Thorax, France (B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Carreau","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Department, Human Research Nutrition Center, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Assistance publique \u2013 H\u00f4pitaux de Paris, Paris, France (V.C., A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sybil","family":"Charri\u00e8re","sequence":"additional","affiliation":[{"name":"F\u00e9d\u00e9ration d\u2019Endocrinologie, Maladies M\u00e9taboliques, Diab\u00e8te et Nutrition, GHE (S.C., P.M.)"},{"name":"Hospices Civils de Lyon, France. CarMen Laboratory, INSERM, INRA, INSA Lyon, Universit\u00e9 Claude Bernard Lyon 1, Pierre-B\u00e9nite, France (O.M., S.C., P.M., N.P., M.D.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u00e9onore","family":"Divry","sequence":"additional","affiliation":[{"name":"Service de Biochimie et Biologie mol\u00e9culaire, Laboratoire de Biologie M\u00e9dicale Multi-Sites (O.M., E.D., M.D.F.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8887-994X","authenticated-orcid":true,"given":"Antonio","family":"Gallo","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Department, Human Research Nutrition Center, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Assistance publique \u2013 H\u00f4pitaux de Paris, Paris, France (V.C., A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Moulin","sequence":"additional","affiliation":[{"name":"Service de Gastroent\u00e9rologie H\u00e9patologie et Nutrition P\u00e9diatrique, HFME (N.P.)"},{"name":"Hospices Civils de Lyon, France. CarMen Laboratory, INSERM, INRA, INSA Lyon, Universit\u00e9 Claude Bernard Lyon 1, Pierre-B\u00e9nite, France (O.M., S.C., P.M., N.P., M.D.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Paillard","sequence":"additional","affiliation":[{"name":"Cardiologie et Maladies vasculaires, Centre Hospitalier de Rennes, France (F.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8359-5163","authenticated-orcid":true,"given":"Noel","family":"Peretti","sequence":"additional","affiliation":[{"name":"F\u00e9d\u00e9ration d\u2019Endocrinologie, Maladies M\u00e9taboliques, Diab\u00e8te et Nutrition, GHE (S.C., P.M.)"},{"name":"Hospices Civils de Lyon, France. CarMen Laboratory, INSERM, INRA, INSA Lyon, Universit\u00e9 Claude Bernard Lyon 1, Pierre-B\u00e9nite, France (O.M., S.C., P.M., N.P., M.D.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1215-1493","authenticated-orcid":true,"given":"Jean-Pierre","family":"Rab\u00e8s","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 Sorbonne Paris Nord, INSERM, LVTS, Paris, France (Y.A.-K., J.-P.R., M.V.)."},{"name":"Laboratoire de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, H\u00f4pital Ambroise Par\u00e9, AP-HP. Universit\u00e9 Paris Saclay, Boulogne-Billancourt, France (J.-P.R.)."},{"name":"UVSQ, UFR Simone Veil- Sant\u00e9, Montigny-Le-Bretonneux, France (J.-P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Varret","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 Sorbonne Paris Nord, INSERM, LVTS, Paris, France (Y.A.-K., J.-P.R., M.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Carri\u00e9","sequence":"additional","affiliation":[{"name":"INSERM UMRS 1166 - ICAN, Faculty of Medicine Pitie-Salp\u00e9tri\u00e8re, Sorbonne University, Paris, France (O.B., A.C.)."},{"name":"Service de Biochimie Endocrinienne et Oncologique, Assistance publique \u2013 H\u00f4pitaux de Paris Sorbonne Universit\u00e9 Piti\u00e9 Salp\u00eatri\u00e8re, Paris, France (O.B., A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6206-5908","authenticated-orcid":true,"given":"Mathilde","family":"Di Filippo","sequence":"additional","affiliation":[{"name":"Service de Biochimie et Biologie mol\u00e9culaire, Laboratoire de Biologie M\u00e9dicale Multi-Sites (O.M., E.D., M.D.F.)"},{"name":"Hospices Civils de Lyon, France. 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