{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T01:57:47Z","timestamp":1772762267175,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFC2500600"],"award-info":[{"award-number":["2021YFC2500600"]}]},{"name":"National Key Research and Development Program of China","award":["2021YFC2500603"],"award-info":[{"award-number":["2021YFC2500603"]}]},{"name":"National Key Research and Development Program of China","award":["82100295"],"award-info":[{"award-number":["82100295"]}]},{"name":"National Key Research and Development Program of China","award":["K202227"],"award-info":[{"award-number":["K202227"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFC2500600"],"award-info":[{"award-number":["2021YFC2500600"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFC2500603"],"award-info":[{"award-number":["2021YFC2500603"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100295"],"award-info":[{"award-number":["82100295"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["K202227"],"award-info":[{"award-number":["K202227"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, Peking University","award":["2021YFC2500600"],"award-info":[{"award-number":["2021YFC2500600"]}]},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, Peking University","award":["2021YFC2500603"],"award-info":[{"award-number":["2021YFC2500603"]}]},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, Peking University","award":["82100295"],"award-info":[{"award-number":["82100295"]}]},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, Peking University","award":["K202227"],"award-info":[{"award-number":["K202227"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Homozygous familial hypercholesterolemia (HoFH) is a rare inborn-errors-of-metabolism disorder characterized by devastatingly elevated low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. The gold standard for screening and diagnosing HoFH is genetic testing. In China, it is expensive and is always recommended for the most likely HoFH subjects with aggressive LDL-C phenotype. However, the LDL-C levels of HoFH patients and a substantial proportion of heterozygous FH (HeFH) patients overlapped considerably. Here, we performed a cost-effective metabolomic profiling on genetically diagnosed HoFH (n = 69) and HeFH patients (n = 101) with overlapping LDL-C levels, aiming to discovery a unique metabolic pattern for screening homozygotes in patients with severe FH. We demonstrated a differential serum metabolome profile in HoFH patients compared to HeFH patients. Twenty-one metabolomic alterations showed independent capability in differentiating HoFH from severe HeFH. The combined model based on seven identified metabolites yielded a corrected diagnosis in 91.3% of HoFH cases with an area under the curve value of 0.939. Collectively, this study demonstrated that metabolomic profiling serves as a useful and economical approach to preselecting homozygotes in FH patients with severe hypercholesterolemia and may help clinicians to conduct selective genetic confirmation testing and familial cascade screening.<\/jats:p>","DOI":"10.3390\/jcm12020483","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T05:57:14Z","timestamp":1673243834000},"page":"483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia"],"prefix":"10.3390","volume":"12","author":[{"given":"Zhiyong","family":"Du","sequence":"first","affiliation":[{"name":"The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China"},{"name":"Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhui","family":"Du","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China"},{"name":"Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linyi","family":"Li","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China"},{"name":"Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haili","family":"Sun","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China"},{"name":"Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaowei","family":"Hu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China"},{"name":"Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-7385","authenticated-orcid":false,"given":"Long","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luya","family":"Wang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China"},{"name":"Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5185-9726","authenticated-orcid":false,"given":"Yanwen","family":"Qin","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, National Clinical Research Center for Cardiovascular Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China"},{"name":"Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/s41569-019-0325-8","article-title":"Familial hypercholesterolaemia: Evolving knowledge for designing adaptive models of care","volume":"17","author":"Watts","year":"2020","journal-title":"Nat. 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