APOE-2基因型对血管疾病患者肥胖与血脂水平关系的影响。

Influence of APOE-2 genotype on the relation between adiposity and plasma lipid levels in patients with vascular disease.

作者信息

Koopal C, van der Graaf Y, Asselbergs F W, Westerink J, Visseren F L J

机构信息

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

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

Int J Obes (Lond). 2015 Feb;39(2):265-9. doi: 10.1038/ijo.2014.105. Epub 2014 Jun 20.

DOI:10.1038/ijo.2014.105

PMID:24946908

Abstract

BACKGROUND

Apolipoprotein E (APOE) genotypes are associated with different plasma lipid levels. People with the APO ɛ2 genotype can develop a disorder called dysbetalipoproteinemia (DBL). A possible predisposing factor for DBL is adiposity. We evaluated whether and to what extent the APOE genotype modifies the relation between adiposity and lipids in patients with manifest arterial disease and we looked at possible determinants of DBL in ɛ2 homo- and heterozygote patients.

METHODS

This prospective cohort study was performed in 5450 patients with manifest arterial disease from the Secondary Manifestations of ARTerial disease (SMART) study. The APOE genotype was measured in all patients and revealed 58 ɛ2 homozygotes, 663 ɛ2 heterozygotes, 3181 ɛ3 homozygotes and 1548 ɛ4 carriers. The main dependent variable was non-high-density lipoprotein cholesterol (non-HDL-c). The relation between adiposity (including body mass index (BMI), waist circumference (waist), visceral adipose tissue (VAT) and metabolic syndrome (MetS)) and lipids was evaluated with linear regression analyses. Determinants of DBL were evaluated using logistic regression.

RESULTS

There was significant effect modification by the APOE genotype on the relation between non-HDL-c and BMI, waist, VAT and MetS. There was an association between BMI and non-HDL-c in ɛ2 homozygotes (β 0.173, 95% confidence interval (CI) 0.031-0.314, P=0.018) and ɛ4 carriers (β 0.033, 95% CI 0.020-0.046, P<0.001). In all genotypes, there was an effect of waist, VAT and MetS on non-HDL-c, but these effects were most distinct in ɛ2 homozygotes (waist β 0.063, 95% CI 0.015-0.110, P=0.011; VAT β 0.580, 95% CI 0.270-0.889, P=0.001; MetS β 1.760, 95% CI 0.668-2.852, P=0.002). Determinants of DBL in ɛ2 homo- and heterozygotes were VAT and MetS.

CONCLUSION

The APOE genotype modifies the relation between adiposity and plasma lipid levels in patients with vascular disease. The relation between adiposity and lipids is present in all patients, but it is most distinct in ɛ2 homozygote patients. Abdominal fat and MetS are determinants of DBL.

摘要

背景

载脂蛋白E（APOE）基因型与不同的血浆脂质水平相关。携带APOε2基因型的人可能会患上一种名为异常β脂蛋白血症（DBL）的疾病。肥胖可能是DBL的一个诱发因素。我们评估了APOE基因型是否以及在何种程度上改变了患有明显动脉疾病患者的肥胖与脂质之间的关系，并研究了ε2纯合子和杂合子患者中DBL的可能决定因素。

方法

这项前瞻性队列研究在来自动脉疾病继发表现（SMART）研究的5450例患有明显动脉疾病的患者中进行。对所有患者进行APOE基因型检测，结果显示有58例ε2纯合子、663例ε2杂合子、3181例ε3纯合子和1548例ε4携带者。主要因变量是非高密度脂蛋白胆固醇（non-HDL-c）。通过线性回归分析评估肥胖（包括体重指数（BMI）、腰围、内脏脂肪组织（VAT）和代谢综合征（MetS））与脂质之间的关系。使用逻辑回归评估DBL的决定因素。

结果

APOE基因型对non-HDL-c与BMI、腰围、VAT和MetS之间的关系有显著的效应修饰作用。在ε2纯合子（β=0.173，95%置信区间（CI）0.031 - 0.314，P = 0.018）和ε4携带者（β=0.033，95% CI 0.020 - 0.046，P < 0.001）中，BMI与non-HDL-c之间存在关联。在所有基因型中，腰围、VAT和MetS对non-HDL-c均有影响，但这些影响在ε2纯合子中最为明显（腰围β=0.063，95% CI 0.015 - 0.110，P = 0.011；VATβ=0.580，95% CI 0.270 - 0.889，P = 0.001；MetSβ=1.760，95% CI 0.668 - 2.852，P = 0.002）。ε2纯合子和杂合子中DBL的决定因素是VAT和MetS。