{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T02:59:18Z","timestamp":1770433158610,"version":"3.49.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2007,4]]},"abstract":"Objective\u2014<\/jats:italic><\/jats:bold>The genetic background of familial combined hyperlipidemia (FCHL) has not been fully clarified. Because several nuclear receptors play pivotal roles in lipid metabolism, we tested the hypothesis that genetic variants of nuclear receptors contribute to FCHL.<\/jats:p>Methods and Results\u2014<\/jats:italic><\/jats:bold>We screened all the coding regions of the PPAR\u03b1, PPAR\u03b32, PPAR\u03b4, FXR, LXR\u03b1, and RXR\u03b3 genes in 180 hyperlipidemic patients including 60 FCHL probands. Clinical characteristics of the identified variants were evaluated in other 175 patients suspected of coronary disease. We identified PPAR\u03b1 Asp140Asn and Gly395Glu, PPAR\u03b32 Pro12Ala, RXR\u03b3 Gly14Ser, and FXR \u22121g\u2212>t variants. Only RXR\u03b3 Ser14 was more frequent in FCHL (15%,P<\/jats:italic><0.05) than in other primary hyperlipidemia (4%) and in controls (5%). Among patients suspected of coronary disease, we identified 9 RXR\u03b3 Ser14 carriers, who showed increased triglycerides (1.62\u00b10.82 versus 1.91\u00b10.42 [mean\u00b1SD] mmol\/L,P<\/jats:italic><0.05), decreased HDL-cholesterol (1.32\u00b10.41 versus 1.04\u00b10.26,P<\/jats:italic><0.05), and decreased post-heparin plasma lipoprotein lipase protein levels (222\u00b185 versus 149\u00b138 ng\/mL,P<\/jats:italic><0.01). In vitro, RXR\u03b3 Ser14 showed significantly stronger repression of the lipoprotein lipase promoter than RXR\u03b3 Gly14.<\/jats:p>Conclusion\u2014<\/jats:italic><\/jats:bold>These findings suggest that RXR\u03b3 contributes to the genetic background of FCHL.<\/jats:p>","DOI":"10.1161\/01.atv.0000258945.76141.8a","type":"journal-article","created":{"date-parts":[[2007,2,3]],"date-time":"2007-02-03T06:46:51Z","timestamp":1170485211000},"page":"923-928","source":"Crossref","is-referenced-by-count":21,"title":["High Frequency of a Retinoid X Receptor \u03b3 Gene Variant in Familial Combined Hyperlipidemia That Associates With Atherogenic Dyslipidemia"],"prefix":"10.1161","volume":"27","author":[{"given":"Atsushi","family":"Nohara","sequence":"first","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masa-aki","family":"Kawashiri","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Claudel","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihoko","family":"Mizuno","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Tsuchida","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutsuko","family":"Takata","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shoji","family":"Katsuda","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Miwa","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Inazu","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. Koizumi), Kanazawa University Hospital, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junji","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"From the Departments of Lipidology (A.N., M.M., J. Kobayashi, H.M.) and Cardiovascular Medicine (M.K., M. Tsuchida, M. Takata, S.K., K.M., M.Y.), Graduate School of Medical Science, Kanazawa University, Japan; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics (T.C., F.K.), University Medical Center Groningen, Groningen, the Netherlands; School of Health Sciences, Faculty of Medicine (A.I.), and Department of General Medicine (J. 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