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

Abstract

Aifan Li,1,* Tianyi Han,2,* Yongfang Li,1 Gaiqing Yang,3 Yuchao Zhang,4 Yanyang Huang,2 Baixue Zhou,2 Guoying Song,2 Ying He2 1Department of Neurology, The First People’s Hospital of Zhengzhou, Zhengzhou, 450000, People’s Republic of China; 2Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 3Department of Geriatric Medicine, the Center Hospital of Zhengzhou Affiliated Zhengzhou University, Zhengzhou, 450004, People’s Republic of China; 4Department of Genetics, First Affiliated Hospital of Xinxiang Medical College, Xinxiang, 453100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying He; Guoying Song, Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China, Tel [phone], Email [email protected]; [email protected] 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

Keywords

• ischemic stroke
• matrix metalloproteinase
• polymorphism
• association study