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基质金属蛋白酶-7血清水平及其基因-181A/G多态性对颈动脉斑块稳定性的影响

Influence of plasma matrix metalloproteinase-7 levels and genetic polymorphism of -181A/G on the stability of carotid plaque

摘要目的 探讨基质金属蛋白酶-7(matrix metalloproteinase-7,MMP-7)血清水平及其基因启动子区-181 A/G多态性对颈动脉斑块稳定性的影响.方法 503例患有颈动脉粥样硬化性疾病的患者根据B型超声检查结果分为颈动脉易损斑块组(118例)和稳定斑块组(385例).采用ELISA法检测两组患者血清MMP-7水平,同时运用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)分析两组患者MMP-7基因启动子-181A/G多态性.结果 易损斑块组血清MMP-7水平为(19.31 ± 8.10)μg/L,而稳定斑块组为(14.98±4.97)μg/L,两者相比差异有统计学意义(t=5.49,P=0.00).MMP-7基因启动子-181位点AG+GG基因型及G等位基因总体分布在易损斑块组和稳定斑块组间比较差异有统计学意义(OR=1.81,P=0.025和OR=1.71,P=0.029).易损斑块组内AG+GG基因型患者血清MMP-7水平较从基因型者高(t=2.62,P=0.01),而稳定斑块组内AG+GG基因型和AA基因型间MMP-7血清水平相比差异无统计学意义(t=6.51,P=0.52).结论 血清MMP-7水平可能成为颈动脉易损斑块检测的一个生物学指标.MMP-7基因启动子区-181A/G多态性可能影响MMP-7蛋白的表达,从而与颈动脉易损斑块的遗传易患性密切相关.

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abstractsObjective To explore the influence of plasma matrix metalloproteinase-7 ( MMP-7 ) levels and genetic polymorphism of MMP-7 - 181 A/G on the stability of carotid plaque.Method According to carotid ultrasound examination, 503 patients with carotid atherosclerotic lesions were consecutively recruited and divided into vulnerable plaque group (n = 118) and stable plaque group (n = 385).Plasma MMP-7 levels were measured by enzyme-linked immunosorbent assay (ELISA), and MMP-7 -181 A/G genotypes were determined by polymerase chain reaction-restiction fragment length polymorphism (PCR-RFLP).Results Plasma MMP-7 levels in carotid vulnerable plaque group were significantly enhanced as compared to stable plaque group (t =5.49, P =0.00).The frequency of MMP-7 -181G allele in vulnerable plaque group was significantly higher than that in stable plaque group (11.4% vs 7.0% ,χ2 = 4.78, P= 0.029).Compared to AA genotype, the genotypes with - 181G allele (AG + GG) significantly increased susceptibility to carotid vulnerable plaque ( χ2 = 5.01, OR = 1.81, P = 0.025 ) .When further analyzing the relationship between genotype and plasma MMP-7 levels, no significant differences of plasma MMP-7 levels were observed between AA genotype and AG + GG genotype in stable plaque group.However, in vulnerable plaque group, plasma MMP-7 levels of AG + GG genotype were significantly higher than that of AA genotype( t = 2.62, P = 0.01).Conclusion The present findings suggest that plasma MMP-7 level may be a biomarker for carotid vulnerable plaque.Genetic polymorphism of - 181 A/G in MMP-7 promoter may affect the expression of MMP-7, and seems to be implicated in susceptibility to carotid vulnerable plaque.

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中华神经科杂志

中华神经科杂志

2011年44卷6期

379-383页

ISTICPKUCSCDCA

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