Guo Tie, Hao Haizhen, Zhou Lv, Zhou Feng, Yu Dan
Haikou Hospital of Xiangya Medical College of Central South University, Haikou, Hainan 570208, China.
Oncotarget. 2017 Dec 18;9(4):4698-4706. doi: 10.18632/oncotarget.23473. eCollection 2018 Jan 12.
Tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) regulates the extracellular matrix degradation, which involved in vascular remodeling and dysfunction, destabilization of atherosclerotic plaque and many other pathological processes. The rupture of atherosclerotic plaque is the trigger of Large artery atherosclerotic (LAA) stroke. We speculate that the Single nucleotide polymorphisms (SNPs) in TIMP-2 may have an association with LAA stroke. To prove this hypothesis, we conducted this case-control study. 250 LAA stroke patients and 250 healthy controls were collected for the analysis of TIMP-2 polymorphisms. Among six SNPs, we detected no deviation from Hardy-Weinberg equilibrium in control group. There was a significant difference in rs4789936 T allele frequency between patient and control groups (OR = 0.68, 95% CI = 0.51-0.91, = 0.009), which means lower risk of LAA stroke. We observed the rs4789936 had a decreased risk of LAA stroke according to the codominant (OR = 0.64, 95% CI = 0.44-0.92, = 0.026), dominant (OR = 0.62, 95% CI = 0.43-0.88, = 0.008), overdominant (OR = 0.68, 95% CI = 0.48-0.98, = 0.039), log-additive (OR = 0.68, 95% CI = 0.51-0.91, = 0.009) models analyses. However, these findings could only validate under dominant model (OR = 0.65, 95% CI = 0.42-1.00, = 0.049) after adjustment of gender and age. The results indicate a potential association between TIMP-2 variants and LAA stroke risk in southern Chinese Han population.
基质金属蛋白酶2组织抑制剂(TIMP-2)调节细胞外基质降解,这一过程涉及血管重塑与功能障碍、动脉粥样硬化斑块不稳定以及许多其他病理过程。动脉粥样硬化斑块破裂是大动脉粥样硬化性(LAA)卒中的触发因素。我们推测TIMP-2中的单核苷酸多态性(SNP)可能与LAA卒中有关。为了验证这一假设,我们开展了这项病例对照研究。收集了250例LAA卒中患者和250例健康对照者,用于分析TIMP-2基因多态性。在六个SNP中,我们在对照组中未检测到偏离哈迪-温伯格平衡的情况。患者组和对照组之间rs4789936 T等位基因频率存在显著差异(OR = 0.68,95% CI = 0.51 - 0.91,P = 0.009),这意味着LAA卒中风险较低。根据共显性(OR = 0.64,95% CI = 0.44 - 0.92,P = 0.026)、显性(OR = 0.62,95% CI = 0.43 - 0.88,P = 0.008)、超显性(OR = 0.68,95% CI = 0.48 - 0.98,P = 0.039)、对数加性(OR = 0.68,95% CI = 0.51 - 0.91,P = 0.009)模型分析,我们观察到rs4789936具有降低LAA卒中风险的作用。然而,在调整性别和年龄后,这些发现仅在显性模型(OR = 0.65,95% CI = 0.42 - 1.00,P = 0.049)下得到验证。结果表明TIMP-2变异与中国南方汉族人群LAA卒中风险之间存在潜在关联。