基质金属蛋白酶3基因rs522616多态性与脑梗死亚型的关系

Correlation between the rs522616 polymorphism in the matrix metalloproteinase-3 and cerebral infarction subtypes

目的探讨基质金属蛋白酶3(MMP-3)血清水平及其启动子区基因rs522616(-709A/G)多态性与低分子肝素试验病因分型(TOAST)中,大动脉粥样硬化性(LAA)和小动脉闭塞性(SAO)卒中的相关性。方法选取289例急性缺血性卒中(发病≤3d)患者,LAA卒中185例,SAO卒中104例,应用酶联免疫吸附法(ELISA)检测血清MMP-3水平,聚合酶链反应后直接测序法检测其启动子基因rs522616多态性。结果①LAA组MMP-3血清水平为(245±56)ng/ml,高于SAO组的(227±51)ng/ml,差异有统计学意义(P<0.01)。②LAA组患者中,MMP-3基因rs522616多态位点AA基因型频率为50.8%,A等位基因频率为71.1%,分别高于SAO组的38.5%和61.5%,差异有统计学意义(P<0.05)。③多因素Logistic回归分析发现,AA基因型(OR=1.72,95%CI:1.04～2.85)和MMP-3(OR=0.014,95%CI:0.00～0.29)水平增高是LAA型卒中的独立危险因子。结论与SAO性卒中比较,MMP-3血清增高水平及rs522616基因多态性位点AA基因型与LAA性卒中关系更为密切。

Objective To investigate the correlation between the serum matrix metalloproteinase-3（MMP-3） level and its rs522616（-709A/G） polymorphism and the Trial of Org 10172 in Acute Stroke Treatment（TOAST） subtypes of ischemic stroke.Methods A total of 289 patients with acute ischemic stroke（symptom onset ≤3 days） were enrolled.They were divided into either a large-artery atherosclerosis（LAA） stroke group（n=185） or a small artery occlusion（SAO） stroke group（n=104） according to the Trial of Org 10172 in Acute Stroke Treatment（TOAST） classification.Enzyme-linked immunosorbent assay（ELISA） was used to detect serum MMP-3 level;after polymerase chain reaction（PCR）,direct sequencing assay was used to detect its promoter gene（rs522616） polymorphism.Results ①The serum MMP-3 level（245±56 ng/mL） in the LAA group was significant higher than that in the SAO group（227±51 ng/mL）.There was significant difference（P0.01）.②Among the patients in the LAA group,the rs522616 gene polymorphism loci AA genotype frequency was 50.8%,the A genotype frequency was 71.1%,and they all higher than those in the SAO group（AA genotype frequency was 38.5%,A genotype frequency was 61.5%）.There was significant difference（P0.05）.③Multivariate logistic regression analysis found that the AA genotype（OR=1.72,95% CI： 1.04-2.85）and MMP-3（OR= 0.014,95% CI：0.00-0.29） were the independent risk factors for LAA stroke.Conclusion Compared to the SAO stroke,the serum MMP-3 level and the rs522616 gene polymorphism loci AA genotype has more close correlation with LAA stroke.