Correlation between Lys45Glu polymorphism of matrix metalloproteinase-3 and ischemic stroke subtypes / 国际脑血管病杂志

ABSTRACT

Objective To investigate the correlation of plasma matrix metalloproteinase-3 (MMP-3)levels and MMP-3 Lys45Glu (rs679620) polyrnorphism with ischemic stroke and its TOAST subtypes.Methods The patients with large artery atherosclerotic stroke (LAA) and small artery occlusion stroke (SAO)according to TOAST etiological typing (ischemic stroke group) and healthy subjects (control group) were enrolled.The enzyme-linked immunosorbent assay was used to detect plasma MMP-3 level.The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes of MMP-3 Lys45Glu.Results A total of 233 patients with ischemic stroke were enrolled,in which 162 were LAA and 71 were SAO; 200 healthy subjects were taken as controls.The plasma MMP-3 level in the ischernic stroke group was significantly higher than that in the control goup (253.99 ± 75.02 ng/ml vs.196.38 ± 78.17 ng/ml;t =7.813,P=0.000).The plasma MMP-3 level in the LAA group (262.81 ±69.23 ng/ml) was significantly higher than those in thegroups of SAO (233.85 ± 83.90 ng/ml,P =0.008) and control (P =0.000),and the plasma MMP-3 level in the SAO was also significantly higher than that in the control group (P =0.000).Multivariate logistic regression analysis showed that the increased serum MMP-3 level was an independent risk factor for ischemic stroke (odds ratio [OR] 1.012,95％ confidence interval [CI] 1.008-1.015; P =0.000).There was no significant difference in the frequencies of genotype (x2 =2.085,P =0.353) and allele (x2 =2.29,P =0.130) of MMP-3 Lys45Glu between the ischemic stroke group and the control group.However,there were significant difference in MMP-3 Lys45Glu genotype frequencies among.the groups of LAA,SAO and control (x2 =10.39,P=0.034).The AA + GA genotype frequency in the LAA group was significant higher than those in the groups of SAO (65.4％ vs.49.3％ ;x2 =5.375,P =0.020) and control (65.4％ vs.54.0％ ;x2 =4.84,P =0.028).There was no significant difference in the allele frequencies among the groups of LAA,SAO and control (x2 =3.887,P =0.143).Multivariate logistic regression analysis showed that MMP-3 Lys45Glu polymorphism was an independent risk factor for LAA (OR 1.783,95％ CI 1.183-2.688; P =0.006).The plasma MMP-3 level in patients with the genotypes AA (n =73),GA (n =176) and GG (n =184)were 235.70 ± 70.85 ng/ml,(244.20 ± 85.90 ng/ml and 207.98 ± 77.61 ng/ml.There were significant difference in the plasma MMP-3 levels among the patients with the genotypes AA,GA and GG (F=9.682,P =0.000).The plasma MMP-3 level in the patients with the genotype AA + GA was significantly higher than that in patients with genotype GG (241.71 ± 81.73 ng/ml vs.207.98 ± 77.61 ng/ml; t =4.336,P =0.000).Conclusions The plasma MMP-3 level increased in patients with LAA or SAO,especially in the patients with LAA.The MMP-3 Lys45Glu polymorphism might be associated with the plasma MMP-3 level and LAA.