MMP-10 rs17435959 Polymorphism is Associated with the Formation and Stability of Carotid Atherosclerosis Plaque: A Case-Control Study

J Stroke Cerebrovasc Dis. 2021 Oct;30(10):106045. doi: 10.1016/j.jstrokecerebrovasdis.2021.106045. Epub 2021 Aug 19.

Abstract

Background: Matrix metalloproteinase 10 (MMP-10) has a close relationship with carotid atherosclerosis (CAS) and cerebral infarction. The MMP-10 rs17435959 polymorphism causes a leucine to valine transition at codon 4 in exon 1 of the MMP-10 gene and may have functional effects.

Objectives: To investigate the relationship between the MMP-10 rs17435959 polymorphism and the formation and stability of CAS plaques.

Materials and methods: The present case-control study contains 738 visitors who came to our health examination center for the first time. According to the carotid ultrasound examinations, visitors were classified into the vulnerable plaque group (41-86 years old, 141 male, 105 female), the stable plaque group (41-86 years old, 141 male, 105 female) and the no plaque group (41-85 years old, 141 male, 105 female). All visitors in the three groups were sex- and- age-matched, and cardiovascular and cerebrovascular diseases were absent. The polymorphism was genotyped by real-time polymerase chain reaction- restriction.

Results: Compared to the GG genotype, the frequency of the CC and CG genotypes was significantly more common in the vulnerable plaque group than in the no plaque group (18.7% vs. 7.7%, unadjusted P = 0.002). Moreover, compared to the G allele, the frequency of the C allele was significantly more common in the vulnerable plaque group than in the no plaque group (10.4% vs. 3.9%, unadjusted P = 0.000) and in the vulnerable plaque group than in the stable plaque group (10.4% vs. 5.1%, unadjusted P = 0.008). Binary logistic regression showed that the CC and CG genotype was independent risk factor for the formation (P = 0.019, OR = 1.961, 95% CI [1.117, 3.444]) and vulnerability (P = 0.035, OR = 1.842, 95% CI [1.045, 3.247]) of CAS plaques. Moreover, individuals who have the C allele showed a higher level of fibrinogen, which was an independent risk factor for the formation of CAS plaques (P = 0.000, OR = 2.425, 95% CI [1.475, 3.985]).

Conclusions: The rs17435959 polymorphism was associated with the formation and vulnerability of CAS plaques. Individuals who had variant-type MMP-10 showed higher levels of fibrinogen, which promoted the formation of CAS plaques.

Keywords: Carotid atherosclerosis plaque; Fibrinogen; Matrix metalloproteinase 10; Polymorphism; Vulnerable plaque.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / enzymology
  • Carotid Artery Diseases / genetics*
  • Case-Control Studies
  • Female
  • Fibrinogen / analysis
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Matrix Metalloproteinase 10 / genetics*
  • Middle Aged
  • Phenotype
  • Plaque, Atherosclerotic*
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Rupture, Spontaneous

Substances

  • Fibrinogen
  • MMP10 protein, human
  • Matrix Metalloproteinase 10