基质金属蛋白酶 9 变体 rs17576 对急性冠脉综合征中缺血性脑卒中风险和严重程度的影响。

Influence of matrix metalloproteinase 9 variant rs17576 on ischemic stroke risk and severity in acute coronary syndrome.

机构信息

Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.

Regional laboratory, Makkah Saudi Arabia.

出版信息

J Stroke Cerebrovasc Dis. 2024 Aug;33(8):107824. doi: 10.1016/j.jstrokecerebrovasdis.2024.107824. Epub 2024 Jun 14.

DOI:10.1016/j.jstrokecerebrovasdis.2024.107824

PMID:38880366

Abstract

BACKGROUND

Ischemic injury is a common mechanism in both ischemic stroke (IS) and acute coronary syndrome (ACS). Matrix metalloproteinase 9 (MMP-9), an endopeptidase that degrades extracellular matrix, is important in the pathogenesis of IS. The purpose of this study is to evaluate the association between the SNP rs17576 in MMP-9 gene with (1) the risk and severity of acute ischemic stroke in Saudi Arab individuals with recent acute coronary syndrome, and (2) the risk of acute coronary syndrome in Saudi Arab individuals without ischemic stroke.

METHODS

A case control study of 200 IS patients, 520 ACS patients (without IS), and 500 aged-matched healthy controls were genotyped to detect the MMP-9 polymorphism rs17156.

RESULTS

Our study demonstrated a non-significant difference in the genotype and allele frequencies of the MMP9 rs17576 polymorphism between the patients with IS and patients with ACS without IS (P = 0.31 for the GA genotype, 0.25 for the AA genotype and P = 0.20 for the A allele). AA genotype was found to be statistically significant between IS and control groups; [OR=1.84, 95 % CI (1.08-3.14), p =0.015]. A allele showed a significant difference between the two groups [OR=1.28, 95 % CI (1.00-1.64), p =0.028]. By comparing ACS without IS and controls, AA genotype was significant [OR=1.46, 95 % CI (1.01-2.12), p =0.029]. Stratification by NIHSS score revealed higher mortality and early neurologic deterioration in IS patients with NIHSS score ≥ 16 (p < 0.001, 0.044 respectively).

CONCLUSION

We deduced the lack of association either with allele or genotype frequencies (p>0.05) between the IS cases and the cases of ACS without IS. In contrast there was a significant association of mutant genotype AA between either the IS group or ACS (without IS) group, and the control group. In addition, different rs17576 genotypes were not associated with raised mortality or a tendency to develop early neurologic deterioration.

摘要

背景

缺血性损伤是缺血性脑卒中（IS）和急性冠状动脉综合征（ACS）的共同发病机制。基质金属蛋白酶 9（MMP-9）是一种降解细胞外基质的内肽酶，在 IS 的发病机制中起重要作用。本研究旨在评估 MMP-9 基因中的 SNP rs17576 与（1）沙特阿拉伯近期急性冠状动脉综合征患者急性缺血性脑卒中的风险和严重程度，以及（2）沙特阿拉伯无缺血性脑卒中患者急性冠状动脉综合征的风险之间的关联。

方法

对 200 例 IS 患者、520 例 ACS 患者（无 IS）和 500 名年龄匹配的健康对照进行病例对照研究，以检测 MMP-9 多态性 rs17156 的基因型。

结果

我们的研究表明，IS 患者和无 IS 的 ACS 患者之间 MMP9 rs17576 多态性的基因型和等位基因频率无显著差异（GA 基因型为 P=0.31，AA 基因型为 P=0.25，A 等位基因为 P=0.20）。AA 基因型在 IS 组和对照组之间有统计学意义；[OR=1.84，95%CI（1.08-3.14），p=0.015]。A 等位基因在两组之间有显著差异[OR=1.28，95%CI（1.00-1.64），p=0.028]。与无 IS 的 ACS 相比，AA 基因型有显著性差异[OR=1.46，95%CI（1.01-2.12），p=0.029]。根据 NIHSS 评分进行分层，发现 NIHSS 评分≥16 的 IS 患者死亡率和早期神经功能恶化更高（p<0.001，0.044）。