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This study was supported by grants PI 18/01777,PI 19/00694 from the Spanish Ministry of Economy and Competitiveness, CIBERCV and Gobierno de Aragon B-14. These projects are co-funded by the Instituto de Salud Carlos III and the European Regional Development Fund (ERDF) of the European UnionA way to make Europe. Biobank of the Aragon HealthSystem (PT17/0015/0039).

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Diagnosis of Familial Dysbetalipoproteinemia Based on the Lipid Abnormalities Driven by APOE2/E2 Genotype

Publicado en:Clinical Chemistry. 69 (2): 140-148 - 2023-02-01 69(2), DOI: 10.1093/clinchem/hvac213

Autores: Bea, Ana M; Cenarro, Ana; Marco-Benedi, Victoria; Laclaustra, Martin; Martin, Cesar; Ibarretxe, Daiana; Pinto, Xavier; Arrobas, Teresa; Vinals, Clara; Civeira, Fernando; Olmos, Salvador

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Background Familial dysbetalipoproteinemia (FDBL) is a monogenic disease due to variants in APOE with a highly variable phenotype. Current diagnostic lipid-based methods have important limitations. The objective is twofold: to define characteristics of dysbetalipoproteinemia (DBL) based on the analysis of APOE in patients from a lipid unit and in a sample from the general population, and to propose a screening algorithm for FDBL. Methods Lipids and APOE genotype from consecutive unrelated subjects from Miguel Servet University Hospital (MSUH) (n = 3603), subjects from the general population participants of the Aragon Workers' Health Study (AWHS) (n = 4981), and selected subjects from external lipid units (Ext) (n = 390) were used to define DBL criteria and to train and validate a screening tool. Results Thirty-five subjects from MSUH, 21 subjects from AWHS, and 31 subjects from Ext were APOE2/2 homozygous. The combination of non high-density lipoprotein cholesterol (non-HDLc)/apoB >= 1.7 plus triglycerides/apoB >= 1.35, in mg/dL (non-HDLc [mmol/L]/apolipoprotein B (apoB) [g/L] >= 4.4 and triglycerides [mmol/L]/apoB [g/L] >= 3.5), provided the best diagnostic performance for the identification of subjects with hyperlipidemia and APOE2/2 genotype (sensitivity 100% in the 3 cohorts, and specificity 92.8% [MSUH], 80.9% [AWHS], and 77.6% [Ext]). This improves the performance of previous algorithms. Similar sensitivity and specificity were observed in APOE2/2 subjects receiving lipid-lowering drugs. Conclusions The combination of non-HDLc/apoB and triglycerides/apoB ratios is a valuable tool to diagnose DBL in patients with hyperlipidemia with or without lipid-lowering drugs. FDBL diagnosis requires DBL and the presence of a compatible APOE genotype. Most adult APOE2/2 subjects express DBL, making FDBL as common as familial hypercholesterolemia in the population.

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