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载脂蛋白B基因的XbaI(rs693)和EcoRI(rs1042031)多态性与2型糖尿病患者的颈动脉斑块相关,但与颈动脉内膜中层厚度无关。

Polymorphisms XbaI (rs693) and EcoRI (rs1042031) of the ApoB gene are associated with carotid plaques but not with carotid intima-media thickness in patients with diabetes mellitus type 2.

作者信息

Nikolajevic Starcevic Jovana, Santl Letonja Marija, Praznikar Zala J, Makuc Jana, Vujkovac Andreja C, Petrovic Daniel

机构信息

Institute of Histology and Embryology, Medical Faculty, University of Ljubljana, Slovenia.

General Hospital Rakičan, Murska Sobota, Slovenia.

出版信息

Vasa. 2014 May;43(3):171-80. doi: 10.1024/0301-1526/a000346.

DOI:10.1024/0301-1526/a000346
PMID:24797048
Abstract

BACKGROUND

Apolipoprotein B is a key structural component of all the atherogenic lipoproteins (LDL, VLDL and IDL). Genetic variations of the ApoB gene may affect plasma ApoB and lipid levels, thus influencing atherogenesis. The present study was designed to investigate the association of polymorphisms XbaI (rs693) and EcoRI (rs1042031) of the ApoB gene with plasma ApoB level, lipid levels and the different ultrasound phenotypes of carotid atherosclerosis in patients with diabetes mellitus type 2.

PATIENTS AND METHODS

595 patients with diabetes (399 on statin therapy and 196 without) and 200 healthy controls were enrolled in the study. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Both XbaI (rs693) and EcoRI (rs1042031) genotypes were determined by real-time PCR.

RESULTS

Genotype distributions and allele frequencies of the XbaI and EcoRI polymorphisms were not statistically significantly different between diabetic patients and controls. No statistically significant difference in lipid parameters, ApoA1, ApoB, hs-CRP and fibrinogen as well as CIMT was observed in diabetic patients regarding XbaI and EcoRI polymorphisms, even after adjustment for statin treatment. The risk of having plaques on carotid arteries was higher in homozygous carriers of the mutant X + allele (OR = 1.74, p = 0.03) and lower in diabetics carrying mutant E- alleles (OR = 0.48, p = 0.02). Neither XbaI nor EcoRI polymorphism was associated with CIMT or presence of unstable plaques in diabetic patients. Plasma ApoB level was not independently associated with any of the ultrasonographic parameters of carotid atherosclerosis.

CONCLUSIONS

Both XbaI and EcoRI polymorphisms were associated with presence of plaques on carotid arteries but not with CIMT or presence of unstable plaques. Plasma ApoB level was not independently associated with ultrasonographic phenotypes of carotid atherosclerosis in patients with diabetes mellitus.

摘要

背景

载脂蛋白B是所有致动脉粥样硬化脂蛋白(低密度脂蛋白、极低密度脂蛋白和中间密度脂蛋白)的关键结构成分。载脂蛋白B基因的遗传变异可能影响血浆载脂蛋白B和脂质水平,从而影响动脉粥样硬化的发生。本研究旨在探讨载脂蛋白B基因XbaI(rs693)和EcoRI(rs1042031)多态性与2型糖尿病患者血浆载脂蛋白B水平、脂质水平及颈动脉粥样硬化不同超声表型之间的关联。

患者与方法

本研究纳入了595例糖尿病患者(399例接受他汀类药物治疗,196例未接受)和200例健康对照。采用超声检查评估颈动脉内膜中层厚度(CIMT)和斑块特征(存在情况和结构)。使用标准生化方法进行生化分析。通过实时聚合酶链反应确定XbaI(rs693)和EcoRI(rs1042031)基因型。

结果

糖尿病患者与对照组之间,XbaI和EcoRI多态性的基因型分布及等位基因频率无统计学显著差异。即使在对他汀类药物治疗进行校正后,糖尿病患者在XbaI和EcoRI多态性方面,脂质参数、载脂蛋白A1、载脂蛋白B、高敏C反应蛋白和纤维蛋白原以及CIMT均无统计学显著差异。突变型X +等位基因的纯合携带者颈动脉出现斑块的风险较高(比值比=1.74,p = 0.03),而携带突变型E -等位基因的糖尿病患者风险较低(比值比=0.48,p = 0.02)。在糖尿病患者中,XbaI和EcoRI多态性均与CIMT或不稳定斑块的存在无关。血浆载脂蛋白B水平与颈动脉粥样硬化的任何超声参数均无独立关联。

结论

XbaI和EcoRI多态性均与颈动脉斑块的存在有关,但与CIMT或不稳定斑块的存在无关。糖尿病患者血浆载脂蛋白B水平与颈动脉粥样硬化的超声表型无独立关联。

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