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

• Published in: VASA Vol. 46; no. 5; p. 363
• Main Authors: Pleskovič, Aleš, Letonja, Marija Šantl, Vujkovac, Andreja Cokan, Starčević, Jovana Nikolajević, Caprnda, Martin, Curilla, Eduard, Mozos, Ioana, Kruzliak, Peter, Prosecky, Robert, Petrovič, Daniel
• Format: Journal Article
• Language: English
• Published: Switzerland 01-08-2017
• Subjects: Aged; Asymptomatic Diseases; Carotid Artery Diseases - diagnostic imaging; Carotid Artery Diseases - enzymology; Carotid Artery Diseases - genetics; Carotid Intima-Media Thickness; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - enzymology; Coronary Artery Disease - genetics; Coronary Stenosis - diagnostic imaging; Coronary Stenosis - enzymology; Coronary Stenosis - genetics; Cross-Sectional Studies; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - genetics; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Linear Models; Male; Matrix Metalloproteinase 3 - genetics; Matrix Metalloproteinase 9 - genetics; Middle Aged; Multivariate Analysis; Phenotype; Polymorphism, Single Nucleotide; Prognosis; Prospective Studies; Risk Factors; Severity of Illness Index; Time Factors; matrix metalloproteinase-3 gene; rs3025058; Carotid atherosclerosis; cross-sectional study; genetic polymorphism; rs17576; rs3918242; matrix metalloproteinase-9 gene
• ISSN: 0301-1526
• DOI: 10.1024/0301-1526/a000637

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.
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.
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).
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.