Evaluation of biochemical algorithms to screen dysbetalipoproteinemia in ε2ε2 and rare APOE variants carriers

Objectives Dysbetalipoproteinemia (DBL) is a combined dyslipidemia associated with an increased risk of atherosclerotic cardiovascular diseases mostly occurring in ε2ε2 subjects and infrequently in subjects with rare APOE variants. Several algorithms have been proposed to screen DBL. In this work, we compared the diagnostic performances of nine algorithms including a new one. Methods Patients were divided into 3 groups according to their APOE genotype: ε2ε2 (“ε2ε2”, n=49), carriers of rare variants (“APOEmut”, n=20) and non-carriers of ε2ε2 nor APOE rare variant (“controls”, n=115). The algorithms compared were those from Fredrickson, Sniderman, Boot, Paquette, De Graaf, Sampson, eSampson, Bea and ours, the “Hospices Civils de Lyon (HCL) algorithm”. Our gold standard was the presence of a ε2ε2 genotype or of a rare variant associated with triglycerides (TG) >1.7 mmol/L. A replication in the UK Biobank and a robustness analysis were performed by considering only subjects with both TG and low-density lipoprotein-cholesterol (LDLc) >90th percentile. Results Total cholesterol (TC)/ApoB and NHDLC/ApoB are the best ratios to suspect DBL. In ε2ε2, according to their likelihood ratios (LR), the most clinically efficient algorithms were the HCL, Sniderman and De Graaf’s. In APOEmut, Sniderman’s algorithm exhibited the lowest negative LR (0.07) whereas the HCL’s exhibited the highest positive LR (29). In both cohorts, the HCL algorithm had the best LR. Conclusions We proposed a powerful algorithm based on ApoB concentration and the routine lipid profile, which performs remarkably well in detecting ε2ε2 or APOE variant-related DBL. Additional studies are needed to further evaluate algorithms performances in DBL carriers of infrequent APOE variants.