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

Abstract

Summary: 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.

Lycopene and Vascular Health

“…IMT is defined by the measurement of the dimension of the intima and media of the arterial wall, whereas a value >0.9 mm is considered abnormal (Cooney et al, 2015 ; Piepoli et al, 2016 ). Although IMT has been considered as a surrogate measure of cardiovascular risk, predicting cardiovascular events, especially myocardial infarction and stroke (O'Leary et al, 1999 ; Touboul, 2015 ; Piepoli et al, 2016 ; Hosseini et al, 2017 ; Pleskovic et al, 2017 ), both the American and the European guidelines on cardiovascular disease prevention do not recommend the systematic measurement of IMT to improve risk assessment (Goff et al, 2014 ; Piepoli et al, 2016 ). Major concerns of IMT include lack of standardization, its high variability and low intra-individual reproducibility (Piepoli et al, 2016 ).…”

Beneficial Effect of Successful Simultaneous Pancreas-Kidney Transplantation on Plasma Profile of Metalloproteinases in Type 1 Diabetes Mellitus Patients

“…MMP-2 and MMP-9 are considered to be main enzymes that degrade collagen type IV, the key component of extracellular matrix that determines the structure of vessels and glomerular base membranes [27]. Previously, the upregulation of MMP-2 and MMP-9 was shown in arterial vasculature of diabetic CKD patients and turned out to be correlated with arterial stiffness [28], whereas a MMP-3 gene polymorphism (rs3025058) was associated with subclinical markers of coronary atherosclerosis and IMT progression in type 2 diabetes [29]. Moreover, several advanced glycation end-products were associated with plasma levels of MMP-2 and MMP-3 in T1D individuals [30].…”

<p>Identification of Hub Genes in Type 2 Diabetes Mellitus Using Bioinformatics Analysis</p>

“…tested the hypothesis that the rs3025058 of the MMP3 gene may be a genetic marker of subclinical carotid and coronary atherosclerosis in patients with T2DM. 34 Van der Leeuw et al evaluated the ability of 23 novel biomarkers representing several pathophysiological pathways to improve the prediction of cardiovascular event (CVE) risk in patients with T2DM. Results presented that MMP3 improved CVE risk prediction in 2 separate cohorts of patients with T2DM beyond traditional risk factors.…”