4.3 Article

MMP9 rs17576 Is Simultaneously Correlated with Symptomatic Intracranial Atherosclerotic Stenosis and White Matter Hyperintensities in Chinese Population

Journal

CEREBROVASCULAR DISEASES
Volume 50, Issue 1, Pages 4-11

Publisher

KARGER
DOI: 10.1159/000511582

Keywords

Symptomatic intracranial atherosclerotic stenosis; White matter hyperintensities; Matrix metalloproteinase 9; Polymorphism

Funding

  1. National Natural Science Foundation of China [81671166, 81400972, xywm2015I30]

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The study aimed to screen for SNPs associated with WMHs in sICAS patients and explore a possible genetic connection between macrovascular disease and small vessel disease. Results showed significant differences in allele frequencies of 88 SNPs between sICAS patients and healthy controls, and 53 SNPs between sICAS patients with and without WMHs. The MMP9 rs17576 was found to be simultaneously associated with sICAS and WMHs. Logistic regression analysis revealed age, hypertension, and MMP9 rs17576 AA genotype as independent risk factors for sICAS with WMHs.
Purpose: The aim of this study was screening for single nucleotide polymorphisms (SNPs) associated with white matter hyperintensities (WMHs) in symptomatic intracranial atherosclerotic stenosis (sICAS) patients and exploring a possible connection in the genetic background between macrovascular disease and small vessel disease. Methods: There were 400 sICAS patients enrolled in the study. Fazekas scores were applied to WMH classification. Healthy controls were referred to 1,000 Genome Project and GeneSky company who provided 1,007 Chinese healthy controls. Fast target sequencing technology was used to select the SNPs of 102 genes related to the pathogenesis of sICAS in the sICAS patients. Results: The allele frequencies of 88 SNPs were significantly different between the sICAS group and the healthy controls (p < 0.05). The allele frequencies of 53 SNPs were significantly different between the sICAS patients with and without WMHs (p < 0.05). Further analysis found that matrix metalloproteinase 9 (MMP9) rs17576 was simultaneously related to sICAS and WMHs. The frequency of the rs17576 A allele was significantly lower in sICAS patients when compared to the normal controls (p = 0.03, OR [95% CI] = 0.75 [0.625-0.91]). Also, the frequency of the rs17576 genotypes was significantly different under codominant (p = 0.009), dominant (p = 0.014), and recessive (p= 0.023) models. The frequency of the rs17576 A allele was significantly higher in sICAS with WMH patients, compared to those without WMHs (p = 0.022, OR [95% CI] = 1.54 [1.06-2.22]); the frequency of the rs17576 genotypes was significantly different under codominant (p = 0.019) and recessive (p = 0.032) models. Logistic regression analysis showed that age, hypertension, and MMP9 rs17576 AA genotype were independent risk factors for sICAS with WMHs. Conclusion: MMP9 rs17576 may be simultaneously associated with the risk of sICAS and WMHs. (c) 2020 S. Karger AG, Basel

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