Paquette Martine, Trinder Mark, Guay Simon-Pierre, Brunham Liam R, Baass Alexis
Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal, Québec H2W 1R7, Canada.
Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6Z 1Y6, Canada.
J Clin Endocrinol Metab. 2025 Feb 18;110(3):e703-e709. doi: 10.1210/clinem/dgae259.
Dysbetalipoproteinemia (DBL) is a multifactorial disorder that disrupts the normal metabolism of remnant lipoproteins, causing increased risk of cardiovascular disease. However, establishing a proper diagnosis is difficult, and the true prevalence of the disease in the general population remains unknown.
The objectives were to study the prevalence of the disease and to validate the performance of different clinical diagnostic criteria in a large population-based cohort.
This study included 453 437 participants from the UK Biobank. DBL was established in participants having an ε2ε2 genotype with mixed dyslipidemia or lipid-lowering therapy use (n = 964). The different diagnostic criteria for DBL were applied in individuals without lipid-lowering medication (n = 370 039, n = 534 DBL), to compare their performance.
Overall, 0.6% of participants had an ε2ε2 genotype, of which 36% were classified as DBL, for a disease prevalence of 0.2% (1:469). The prevalence of DBL was similar between the different genetic ancestries (≤0.2%). Several diagnostic criteria showed good sensitivity for the diagnosis of DBL (>90%), but they suffered from a very low positive predictive value (0.6-15.4%).
This study reported for the first time the prevalence of DBL in the UK Biobank according to genetic ancestry. Furthermore, we provided the first external validation of different diagnostic criteria for DBL in a large population-based cohort and highlighted the fact that these criteria should not be used to diagnose DBL alone but should rather be used as a first screening step to determine which individuals may benefit from genetic testing to confirm the diagnosis.
异常β脂蛋白血症（DBL）是一种多因素疾病，会扰乱残余脂蛋白的正常代谢，增加心血管疾病风险。然而，进行准确诊断很困难，该疾病在普通人群中的真实患病率仍然未知。
本研究旨在探讨该疾病的患病率，并在一个大型人群队列中验证不同临床诊断标准的性能。
本研究纳入了英国生物银行的453437名参与者。DBL定义为具有ε2ε2基因型且伴有混合性血脂异常或使用降脂治疗的参与者（n = 964）。将DBL的不同诊断标准应用于未使用降脂药物的个体（n = 370039，其中534例为DBL），以比较其性能。
总体而言，0.6%的参与者具有ε2ε2基因型，其中36%被归类为DBL，疾病患病率为0.2%（1:469）。不同遗传血统之间的DBL患病率相似（≤0.2%）。几种诊断标准对DBL的诊断具有较高的敏感性（>90%），但阳性预测值非常低（0.6 - 15.4%）。
本研究首次报告了英国生物银行中按遗传血统划分的DBL患病率。此外，我们在一个大型人群队列中首次对DBL的不同诊断标准进行了外部验证，并强调这些标准不应单独用于诊断DBL，而应作为初步筛查步骤，以确定哪些个体可能从基因检测中受益以确诊疾病。
