载脂蛋白 E ε2 纯合子人群中肥胖与血脂异常发展的相关性：两项基于人群队列的纵向分析。

Adiposity and the development of dyslipidemia in APOE ε2 homozygous subjects: A longitudinal analysis in two population-based cohorts.

机构信息

Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, the Netherlands.

Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.

出版信息

Atherosclerosis. 2021 May;325:57-62. doi: 10.1016/j.atherosclerosis.2021.04.001. Epub 2021 Apr 3.

DOI:10.1016/j.atherosclerosis.2021.04.001

PMID:33892328

Abstract

BACKGROUND AND AIMS

Familial dysbetalipoproteinemia (FD), characterized by remnant lipoprotein accumulation and premature cardiovascular disease, occurs in homozygous carriers of the APOE ε2 allele, but genetic predisposition alone does not suffice for the clinical phenotype. Cross-sectional studies suggest that a second metabolic hit - notably adiposity or insulin resistance - is required, but the association between these risk factors and development of FD has not been studied prospectively.

METHODS

For this study, we evaluated 18,987 subjects from two large prospective Dutch population-based cohorts (PREVEND and Rotterdam Study) of whom 118 were homozygous APOE ε2 carriers. Of these, 69 subjects were available for prospective analyses. Dyslipidemia - likely to be FD - was defined as fasting triglyceride (TG) levels >3 mmol/L in untreated subjects or use of lipid lowering medication. The effect of weight, body mass index (BMI), waist circumference, type 2 diabetes mellitus and non-TG metabolic syndrome on development of dyslipidemia was investigated.

RESULTS

Eleven of the 69 ε2ε2 subjects (16%) developed dyslipidemia - likely FD - during follow-up. Age-, sex- and cohort-adjusted risk factors for the development of FD were BMI (OR 1.19; 95%CI 1.04-1.39), waist circumference (OR 1.26 95%CI 1.01-1.61) and presence of non-TG metabolic syndrome (OR 4.39; 95%CI 1.04-18.4) at baseline. Change in adiposity during follow-up was not associated with development of dyslipidemia.

CONCLUSIONS

Adiposity increases the risk of developing an FD-like lipid phenotype in homozygous APOE ε2 subjects. These results stress the importance of healthy body weight in subjects at risk of developing FD.

摘要

背景与目的

家族性载脂蛋白 B 代谢障碍（FD）的特征是残粒脂蛋白积聚和早发心血管疾病，发生于载脂蛋白 E ε2 等位基因纯合子携带者，但遗传易感性本身并不足以导致临床表型。横断面研究表明，需要第二个代谢打击——特别是肥胖或胰岛素抵抗，但这些危险因素与 FD 的发生之间的关联尚未前瞻性研究。

方法

在这项研究中，我们评估了来自两个大型前瞻性荷兰人群队列（PREVEND 和鹿特丹研究）的 18987 名受试者，其中 118 名是载脂蛋白 E ε2 纯合子携带者。在这些人中，有 69 名受试者可进行前瞻性分析。血脂异常——可能是 FD——定义为未经治疗的受试者空腹甘油三酯（TG）水平>3mmol/L 或使用降脂药物。研究了体重、体重指数（BMI）、腰围、2 型糖尿病和非 TG 代谢综合征对血脂异常发展的影响。

结果

在 69 名 ε2ε2 受试者中，有 11 名（16%）在随访期间发生血脂异常——可能是 FD。在调整年龄、性别和队列后，FD 发病的危险因素为 BMI（OR 1.19；95%CI 1.04-1.39）、腰围（OR 1.26；95%CI 1.01-1.61）和基线时存在非 TG 代谢综合征（OR 4.39；95%CI 1.04-18.4）。随访期间的肥胖变化与血脂异常的发生无关。