Correlation between matrix metalloproteinase-2 polymorphisms and first and recurrent atherosclerotic ischemic stroke events: a case–control study

Abstract

Objective To determine the associations between matrix metalloproteinase-2 (MMP-2, encoded by the MMP2 gene) 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke in a Chinese population. Methods Patients with first and recurrent ischemic stroke were included. Serum MMP-2 was measured, and MMP2 1306C/T and 735C/T polymorphisms were detected. The associations between MMP2 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke were analyzed. Results Serum MMP-2 in patients with first and recurrent ischemic stroke was significantly higher compared with controls, and patients with recurrent ischemic stroke had higher MMP-2 than those with first ischemic stroke. The frequency of the CC genotype and C allele of MMP2 735C/T was highest in patients with recurrent ischemic stroke, followed by patients with first ischemic stroke, and controls. Conversely, the genotype and allele of MMP2 1306C/T did not significantly differ between groups. The CC genotype of MMP2 735C/T was independently associated with first and recurrent ischemic stroke (odds ratios = 1.45 and 1.64, respectively), as was the C allele of MMP2 735C/T (odds ratios = 1.68 and 1.77, respectively). Conclusions The CC genotype and C allele of MMP2 735C/T were associated with first and recurrent ischemic stroke in a Chinese population.

Impact of MMP2 rs243849 and rs14070 genetic polymorphisms on the ischemic stroke susceptibility in Chinese Shaanxi population

“…The regulatory role of MMP2 may be related to the regulation of its genetic variation. Li et al ( 13 ) illustrated that compared with the normal control group, the frequency of CC genotype and C allele of MMP2 735C/T in the first and recurrent IS in the Chinese population were significantly increased, and the frequency of IS recurrence was more significant. Previous studies demonstrated that rs243849 in MMP2 evidently reduced the risk of IS in Hainan population, while rs1053605 in MMP2 was not found to be associated with IS susceptibility ( 9 ).…”

“…In this study, only 3 SNPs in MMP2 were explored, and we will continue to explore the association of other SNPs in MMP2 , MMPs and gene interactions with IS susceptibility in the future ( 16 ). Additionally, the current study was limited to a single ethnic group, other ethnic groups should be validated in the future ( 13 , 17 ). Finally, in order to further determine the potential impact of MMP2 genetic variation on the risk of IS, cell and animal models will be required to verify its regulatory mechanism in different stages of IS ( 2 ).…”

“…Inflammation can not only promote thrombus formation and improve the stability of thrombus, but also damage the blood-brain barrier (BBB) ( 12 ). Matrix metalloproteinases (MMPs), as a class of proteolytic zinc-dependent enzymes, can regulate cytokines ( 13 ), angiogenesis ( 10 ), extracellular matrix (ECM) degradation ( 14 ), and cause BBB disorders ( 4 ), which affect the pathogenesis of vascular inflammation, stroke and atherosclerosis ( 11 ). It has been reported that the MMPs associated with IS were mainly concentrated in MMP2 and MMP9 ( 15 ).…”

“…It has been reported that the MMPs associated with IS were mainly concentrated in MMP2 and MMP9 ( 15 ). MMP2 also regulates angiogenesis, vascular inflammation, ECM degradation, and BBB disruption, which are critical to IS occurrence, progression, and recovery ( 13 ). Genetic polymorphisms of MMP2 affect its transcription and expression ( 10 ), a preliminary study found that rs1132896 and rs243849 of MMP2 evidently reduced the risk of IS in southern Chinese populations ( 9 ).…”

MMP9 SNP and MMP SNP–SNP interactions increase the risk for ischemic stroke in the Han Hakka population

“…Previous studies have shown that gene polymorphisms play an important role in atherosclerotic IS (Malik et al., 2018 ). In recent years, people have become increasingly interested in the study of matrix metalloproteinases (MMPs) and their relationship with the pathogenesis of atherosclerotic cerebrovascular disease (Chehaibi et al., 2014 ; Li et al., 2021 ; Wang & Khalil, 2018 ).…”