Polymorphisms of the Matrix Metalloproteinase Genes are Associated with Acute Ischemic Stroke in Chinese Han Population

Abstract

Background and Purpose

Studies have shown that matrix metalloproteinase (MMP-2,3,9) plays an important role in the pathologic process of ischemic stroke (IS). The aim of this study was to investigate the relationship between C1306T, 1612–5A/6A, C-1562T polymorphisms of MMP-2,3,9 genes and IS in Chinese Han population.

Methods

The polymorphisms of MMP-2(C1306T), −3(1612–5A/6A), −9(C-1562T) gene were detected by PCR-RFLP and SNaPshot sequencing. Then, stratified analysis was used to study the relationship between IS subtypes and MMP-2,3,9 polymorphisms.

Results

For the MMP-2 gene C1306T polymorphism, TT genotype and T allele were significantly associated with a reduced risk of IS (P = 0.015, P = 0.003, respectively). T allele was significantly associated with a reduced risk of small artery occlusion (SAO) subtype compared with the control group (P = 0.012, OR = 0.550, 95% CI = 0.065–1.291). For the MMP-3 gene-1612 (5A/6A) polymorphism, 5A/5A genotype was significantly increased in the IS group (P = 0.011, OR = 0.370, 95% CI = 0.168–0.814), especially in the large-artery atherosclerosis (LAA) subtype (P = 0.001, OR = 2.345) as compared to the control group.

Conclusion

Our study suggested that the T allele of MMP-2 may be a protective factor of IS, especially in SAO subtype, while the 5A/5A gene of MMP-3 may increase the risk of IS, especially in LAA subtype in Chinese Han population.

Keywords:

• ischemic stroke
• matrix metalloproteinase
• polymorphism
• association study

Abbreviations

95% CI, 95% confidence intervals; HWE, Hardy–Weinberg equilibrium; AIS, acute ischemic stroke; LAA, large-artery atherosclerosis; SAO, small artery occlusion; SOE, stroke of other determined cause; MMPs, matrix metalloproteinases; ORs, odds ratios; SNP, single nucleotide polymorphism.

Ethics Approval and Consent to Participate

The study protocols were in line with the tenets of the Declaration of Helsinki and approved by the Ethics Committee on Human Research of Zhengzhou University and informed written consent was obtained from each participant. All experiments were performed in accordance with relevant guidelines and regulations.

Acknowledgments

We acknowledge the technical assistance of staff members of the department of Neurology of First People's Hospital of Zhengzhou. We also thank all patients and controls for providing blood samples.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

The research reported in this publication was supported by the National Natural Science Foundation of China (grant no. U2004114).