基质金属蛋白酶-3基因多态性（rs3025058）影响2型糖尿病患者的动脉粥样硬化标志物。

Matrix metalloproteinase-3 gene polymorphism (rs3025058) affects markers atherosclerosis in type 2 diabetes mellitus.

作者信息

Pleskovič Aleš, Letonja Marija Šantl, Vujkovac Andreja Cokan, Starčević Jovana Nikolajević, Caprnda Martin, Curilla Eduard, Mozos Ioana, Kruzliak Peter, Prosecky Robert, Petrovič Daniel

机构信息

1 Department of Cardiology, University Medical Centre, University of Ljubljana, Ljubljana, Slovenia.

2 General Hospital Rakičan, Murska Sobota, Slovenia.

出版信息

Vasa. 2017 Aug;46(5):363-369. doi: 10.1024/0301-1526/a000637. Epub 2017 May 19.

DOI:10.1024/0301-1526/a000637

PMID:28521653

Abstract

BACKGROUND

The study was designed to test the possible association between either polymorphisms of the matrix metalloproteinase-9 (MMP-9) gene (rs17576, rs3918242) or the MMP-3 5A/6A gene polymorphism (rs3025058) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The second aim of the study was to demonstrate an association between either the rs17576, rs3918242 or rs3025058 and subclinical markers of coronary artery disease in the same subset of patients with T2DM.

PATIENTS AND METHODS

A total of 595 subjects with T2DM and 200 subjects without T2DM (control group) were enrolled in the prospective study. Subclinical markers of carotid atherosclerosis were assessed ultrasonographically. Additionally, in a subset of subjects with T2DM a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of all three polymorphisms (rs17576, rs3918242, rs3025058) was performed with real-time PCR systems.

RESULTS

The comparison of atherosclerosis parameters was performed with regard to different genotypes of MMP-9 rs17576, rs3918242, and MMP-3 rs3025058 polymorphisms upon enrolment and during follow-up. In our study, we found an association between the MMP-3 rs3025058 and CIMT at the time of recruitment. Multiple linear regression analysis revealed the association of either the A- allele or the A- genotypes of the rs3025058 (MMP-3) with carotid intima media thickness (CIMT) progression in a 3.8-year follow-up. We demonstrated the effect of the rs3025058 on subclinical markers of coronary atherosclerosis (coronary calcium score, number of coronary arteries with more than 50 % stenosis, and presence of at least one vessel with more than 50 % stenosis).

CONCLUSIONS

We found an association between the MMP-3 rs3025058 and subclinical markers of carotid (CIMT) and coronary atherosclerosis at the time of recruitment. Moreover, we demonstrated the effect of the MMP-3 rs3025058 on CIMT progression in the 3.8-year follow-up in patients with T2DM.

摘要

背景

本研究旨在检测基质金属蛋白酶-9（MMP-9）基因多态性（rs17576、rs3918242）或MMP-3 5A/6A基因多态性（rs3025058）与2型糖尿病（T2DM）患者颈动脉粥样硬化标志物之间可能存在的关联。本研究的第二个目的是证明rs17576、rs3918242或rs3025058与同一组T2DM患者冠状动脉疾病亚临床标志物之间的关联。

患者与方法

共有595例T2DM患者和200例非T2DM患者（对照组）纳入本前瞻性研究。通过超声检查评估颈动脉粥样硬化的亚临床标志物。此外，对一部分T2DM患者进行冠状动脉计算机断层扫描血管造影（CCTA）以用于诊断目的。使用实时PCR系统对所有三种多态性（rs17576、rs3918242、rs3025058）进行基因分型。

结果

在入组时和随访期间，针对MMP-9 rs17576、rs3918242以及MMP-3 rs3025058多态性的不同基因型对动脉粥样硬化参数进行了比较。在我们的研究中，我们发现在招募时MMP-3 rs3025058与颈动脉内膜中层厚度（CIMT）之间存在关联。多元线性回归分析显示，在3.8年的随访中，rs3025058（MMP-3）的A等位基因或A基因型与颈动脉内膜中层厚度（CIMT）进展相关。我们证明了rs3025058对冠状动脉粥样硬化亚临床标志物（冠状动脉钙化评分、狭窄超过50%的冠状动脉数量以及至少有一条血管狭窄超过50%的情况）的影响。