APOB to Estimated APOB Ratio for Screening for the APOE2 Genotype

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.

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.

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)].

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.