Key result
MMP-9 rs17576 AA genotype linked to ~84% higher ischemic stroke risk vs controls.
Why the study?
Ischemic injury is a common mechanism in both ischemic stroke and acute coronary syndrome, and MMP-9 is important in the pathogenesis of ischemic stroke, prompting evaluation of the MMP-9 SNP rs17576.
Is the MMP-9 variant rs17576 associated with ischemic stroke risk in patients with acute coronary syndrome or ACS risk in healthy individuals?
Case-Control (n=1,220)
Is the MMP-9 variant rs17576 associated with ischemic stroke risk in patients with acute coronary syndrome or ACS risk in healthy individuals?
Odds Ratio: 1.84 (95% CI 1.08–3.14)
p-value: p=0.015
The MMP-9 rs17576 AA genotype is associated with an increased risk of both ischemic stroke and acute coronary syndrome compared to healthy controls in a Saudi Arab population, but does not differentiate stroke risk among ACS patients.
rs17576 AA genotype was associated with ischemic stroke risk; hypothesis-generating in Saudi Arabs and requires validation before any clinical use.
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.
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Bogari et al. (2024) conducted a case-control in Ischemic stroke and acute coronary syndrome (n=1,220). MMP-9 polymorphism rs17576 vs. Healthy controls was evaluated on Risk of ischemic stroke (AA genotype vs controls) (OR 1.84, 95% CI 1.08-3.14, p=0.015). The MMP-9 rs17576 AA genotype was significantly associated with an increased risk of ischemic stroke compared to healthy controls (OR 1.84; 95% CI 1.08-3.14; p=0.015).
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