Expression Of Matrix Metalloproteinases-1,2 And Gene Polymorphism In Patients With Acute Cerebral Infarction And Their Effect On Prognosis

[Objective] To investigate the effects of matrix metalloproteinase-1 and matrix metalloproteinase-2(MMP-1 and MMP-2)levels,gene polymorphism and gene interaction on the prognosis of acute cerebral infarction.[Methods] A total of 332 patients with acute cerebral infarction were collected continuously,and 263 subjects from the same physical examination center were regarded as healthy control group.According to the score of modified Rankin Scale(m RS),the patients in cerebral infarction group were divided into two groups: good prognosis group(m RS ≤ 2)and poor prognosis group(m RS > 2)after 90 days.The levels of MMP-1 and MMP-2 were detected in all patients by enzyme-linked immunosorbecy assay(ELISA),and four single nucleotide gene loci of MMP-1:rs1799750,MMP-2: rs243865,rs2285053 and rs2241145 were detected by flight mass spectrometry.The levels of MMP-1,MMP-2 and four SNPs were compared between the acute cerebral infarction group and the control group.The differences of MMP-1,MMP-2 and four SNPs between the two groups were compared.The generalized multifactor dimensionality reduction(GMDR)betav0.7 software was used to analyze the role of gene interaction in patients with cerebral infarction.Logistic regression was used to analyze the risk factors of cerebral infarction.[Results] 1.There was no significant statistical differences in smoking and drinking between the cerebral infarction group and the healthy control group(P > 0.05).But the incidence of male in cerebral infarction group was higher.The proportion of the age of the cerebral infarction group,hypertension,diabetes,total cholesterol,low-density lipoprotein cholesterol,homocysteine,MMP 1,MMP-2 expression levels were higher than those in the control group,the difference was statistically significant(P < 0.05);while the high density lipoprotein in the cerebral infarction group was lower than that in the control group,the difference was statistically significant(P<0.05).There was no statistically significant difference in triglyceride and uric acid between the two groups(P >0.05).2.There was significant difference in MMP-2 rs243865 gene polymorphism between cerebral infarction group and control group(P < 0.05),but there was no significant difference in MMP-1: rs1799750,MMP-2: rs2285053,rs2241145 gene polymorphism between the two groups(P >0.05).3.Logistic regression analysis showed that age,hypertension,diabetes,total cholesterol,low density lipoprotein,MMP-1 and MMP-2 were independent risk factors for cerebral infarction(P < 0.05).The mutation of MMP-2 rs243865 T site was positively correlated with the disease.Compared with CC type without mutation,the incidence of CT type cerebral infarction increased,the corresponding OR(95% CI)was 1.328(0.086-1.347),but there was no statistical significance(P > 0.05);compared with CC type without mutation,the incidence of TT type cerebral infarction increased,the corresponding OR(95% CI)was 5.162(1.113-23.951),there was statistical significance(P < 0.05).4.GMDR analysis showed that rs243865 and rs1799750 gene interaction model was the best combination of susceptibility to cerebral infarction,the consistency of cross test was 10/10,the accuracy of sample test was 54.34%,P = 0.0107,and increased the incidence of cerebral infarction(OR:1.591,95% CI: 1.351-1.994).5.The serum MMP-1 and MMP-2 levels in the poor prognosis group were significantly higher than those in the good prognosis group at admission after 90 days follow-up of cerebral infarction,with statistical significance(P <0.05).Logistic regression analysis showed that MMP-1 level(OR: 7.198,95%CI:2.541-20.391)and MMP-2 level(OR: 13.335,95%,CI: 5.353-33.219)were independent risk factors for poor prognosis of patients with cerebral infarction at 90 days.[Conclusion] The expression levels of MMP-1 and MMP-2 were increased in acute stage of cerebral infarction,which were related to the 90 days prognosis of cerebral infarction;The mutation of MMP-2 rs243865 C/T site increases the susceptibility to cerebral infarction,and the interaction with MMP-1 rs1799750 significantly increases the risk of cerebral infarction.