Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia
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, i...
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MDPI AG
2023-01-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/2/483 |
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| author | Zhiyong Du Yunhui Du Linyi Li Haili Sun Chaowei Hu Long Jiang Luya Wang Yanwen Qin |
| author_facet | Zhiyong Du Yunhui Du Linyi Li Haili Sun Chaowei Hu Long Jiang Luya Wang Yanwen Qin |
| author_sort | Zhiyong Du |
| collection | DOAJ |
| description | 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 (<i>n</i> = 69) and HeFH patients (<i>n</i> = 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. |
| first_indexed | 2024-03-09T12:12:39Z |
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| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T12:12:39Z |
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| spelling | doaj.art-36bf8b1994de457ea33f0dd1d75312472023-11-30T22:50:34ZengMDPI AGJournal of Clinical Medicine2077-03832023-01-0112248310.3390/jcm12020483Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial HypercholesterolemiaZhiyong Du0Yunhui Du1Linyi Li2Haili Sun3Chaowei Hu4Long Jiang5Luya Wang6Yanwen Qin7The 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, ChinaThe 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, ChinaThe 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, ChinaThe 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, ChinaThe 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, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, ChinaThe 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, ChinaThe 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, ChinaHomozygous 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 (<i>n</i> = 69) and HeFH patients (<i>n</i> = 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.https://www.mdpi.com/2077-0383/12/2/483homozygous familial hypercholesterolemiasevere heterozygous familial hypercholesterolemiametabolomicsdiagnostic markers |
| spellingShingle | Zhiyong Du Yunhui Du Linyi Li Haili Sun Chaowei Hu Long Jiang Luya Wang Yanwen Qin Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia Journal of Clinical Medicine homozygous familial hypercholesterolemia severe heterozygous familial hypercholesterolemia metabolomics diagnostic markers |
| title | Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia |
| title_full | Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia |
| title_fullStr | Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia |
| title_full_unstemmed | Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia |
| title_short | Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia |
| title_sort | metabolomic approach to screening homozygotes in chinese patients with severe familial hypercholesterolemia |
| topic | homozygous familial hypercholesterolemia severe heterozygous familial hypercholesterolemia metabolomics diagnostic markers |
| url | https://www.mdpi.com/2077-0383/12/2/483 |
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