Key result
Measured to estimated APOB ratio accurately identifies APOE2 genotype with ~0.99 AUC.
Why the study?
Does the APOB to estimated APOB ratio improve the identification of the APOE ɛ2/ɛ2 genotype compared to other lipid tests in a primary prevention cohort?
Cohort (n=298,249)
Does the APOB to estimated APOB ratio improve the identification of the APOE ɛ2/ɛ2 genotype compared to other lipid tests in a primary prevention cohort?
Answers are grounded in this paper and cite their sources.
The APOB to estimated APOB ratio provides a highly accurate method using routinely available lipid tests to screen for the APOE ɛ2/ɛ2 genotype, which is associated with familial dysbetalipoproteinemia.
BACKGROUND: Familial dysbetalipoproteinemia (FDB) is a genetic lipoprotein disorder that can develop in patients homozygous for the apolipoprotein 2 (APOE2) genotype (APOE ɛ2/ɛ2). It is associated with decreased clearance of remnant lipoproteins and increased atherosclerotic cardiovascular disease (ASCVD) risk disproportionate to low-density lipoprotein-cholesterol level. A goal of this study was to develop a screening test for the ɛ2/ɛ2 genotype based on routinely available lipid tests and to determine those at most risk for ASCVD. MATERIALS AND METHODS: After assembly of a primary prevention cohort from the UK Biobank (n = 298 249), gene array and exome data were utilized to classify patients as being ɛ2/ɛ2 genotype positive or negative. Lipid profiles and apolipoprotein B (APOB) levels were extracted and the number of ASCVD events was tabulated during a 15-year follow-up period. RESULTS: Using a newly developed equation for estimating APOB (eAPOB) with lipid panel test results, the ratio of measured APOB to eAPOB was better than any other individual lipid test or ratio for identifying patients with the ɛ2/ɛ2 genotype [area under the curve (AUC): APOB/eAPOB: 0.990 (0.986-0.994), nonhigh-density lipoprotein cholesterol/APOB: 0.961 (0.952-0.970), APOB: 0.955 (0.949-0.961), very low-density lipoproteins/triglycerides: 0.788 (0.771-0.804)]. Most ɛ2/ɛ2 patients could be identified with the APOB/eAPOB ratio regardless of their FDB phenotype status. The PCE or PREVENT risk equations were the most accurate method for identifying higher risk patients [AUC: PREVENT: 0.690 (0.637-0.742), PCE: 0.697 (0.645-0.749)]. CONCLUSION: The APOB/eAPOB ratio can be used to accurately identify the ɛ2/ɛ2 genotype and conventional risk equations are the best method for determining those at risk for ASCVD.
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Auger et al. (2026) conducted a cohort in Familial dysbetalipoproteinemia (FDB) / APOE2 genotype (n=298,249). APOB to estimated APOB (eAPOB) ratio vs. Other individual lipid tests or ratios was evaluated on Identifying patients with the ɛ2/ɛ2 genotype (AUC 0.990, 95% CI 0.986-0.994). The APOB to estimated APOB ratio accurately identified patients with the APOE2 genotype (AUC 0.990; 95% CI 0.986-0.994), outperforming other individual lipid tests or ratios.
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