Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

Abstract

Background: Matrix metalloproteinases (MMP) are expressed after ischemic stroke. These proteases are responsible for a higher incidence of hemorrhages, are correlated to size of infarction and influence the effects of recombinant tissue plasminogen activator treatment. We therefore evaluated single nucleotide polymorphisms (SNP) of MMP-2 in different subtypes of stroke patients in an association study using a case-control design. Methods: 197 stroke patients were divided according to modified TOAST criteria (small vessel disease, large vessel disease, hemorrhagic stroke and asymptomatic carotid artery stenosis) and compared to 143 controls. Clinical data like age, sex, risk factors and diagnostic results including MRI or cranial CT scans and ultrasound evaluations of intra- and extracranial arteries were obtained. Genotypes of MMP-2 (12 SNP) were compared to controls and DNA samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis. Logistic regression analysis was performed for small vessel disease to test for interactions between markers and defined clinical risk factors. Additionally, MMP-2 serum levels obtained in the first 24 h after stroke were measured. Results: From the MMP-2 gene, 5 markers (rs1030868, rs2241145, rs2287074, rs2287076, rs7201) showed a significant association with small vessel infarcts (p < 0.05) and rs7201:g.C was identified as an independent risk factor by multivariable logistic regression analysis. MMP-2 protein levels were significantly lower in this group (174 ± 48 ng/dl) versus controls (214 ± 56 ng/dl). For other stroke subtypes, no significant association with MMP-2 SNP could be found. Conclusion: Our study demonstrates an association of the MMP-2 gene with the development of lacunar stroke, and no association of MMP-2 with other stroke subtypes.

Association of a Genetic Variant in the <i>ALOX5AP</i> with Higher Risk of Ischemic Stroke: A Case-Control, Meta-Analysis and Functional Study

“…Most studies published as a follow-up to the original article present limitations in the number of variants tested, small size of samples analyzed and the subtyping of the different etiologies of stroke [31,32]. In our case, technical difficulties prevented the analysis of more variants, including the other SNPs constituting the HapA haplotype of the ALOX5AP gene, as well as the AC008818-1 microsatellite in the PDE4D gene, which were associated with stroke in the initial paper.…”

Polymorphisms Associated with Both Noncardioembolic Stroke and Coronary Heart Disease: Vienna Stroke Registry

“…Only patients with noncardioembolic stroke (defined as ischemic stroke that was not of cardioembolic origin) were included as cases in this study since cardioembolic stroke involves distinct disease mechanisms, such as atrial fibrillation or heart valve disease, which are not common mechanisms of noncardioembolic stroke or CHD [6, 7]. In addition, there is evidence that some genetic variants may be associated with specific stroke subtypes [8, 9]. Controls were unrelated Caucasian participants in a health care program in Vienna, 45 years old or older, free of arterial vascular disease, and reported no arterial vascular diseases in first-degree relatives [5].…”

TIMP-2 Gene Polymorphism Is Associated with Intracerebral Hemorrhage

“…During the past years different single-nucleotide polymorphisms (SNPs) and their association with cerebrovascular diseases were studied. Our group reported several SNPs in the MMP-2 gene, one of them is associated with lacunar stroke [13]. Our aim was to identify relevant SNPs in the coding region of TIMP-2 and how they contribute to the incidence of IS and ICH.…”