基质金属蛋白酶-1和基质金属蛋白酶-3基因变异与缺血性中风及其亚型的关联
Association of Matrix Metalloproteinase-1 and Matrix Metalloproteinase-3 Gene Variants with Ischemic Stroke and Its Subtype.
作者信息
Huang Xiao-Ya, Han Li-Ya, Huang Xiang-Dong, Guan Chao-Hong, Mao Xin-Lei, Ye Zu-Sen
机构信息
Department of Neurology, Wenzhou Central Hospital & Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
出版信息
J Stroke Cerebrovasc Dis. 2017 Feb;26(2):368-375. doi: 10.1016/j.jstrokecerebrovasdis.2016.09.034. Epub 2016 Oct 25.
BACKGROUND
Genetic variations in the genes of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of ischemic stroke (IS). Here we investigate the association between MMP-1 -1607 1G/2G and MMP-3 -1171 5A/6A genetic polymorphisms and etiological subtypes of IS in the Han Chinese population.
METHODS
A total of 640 eligible patients with IS and 637 age- and gender-matched apparently healthy volunteers were enrolled. Subtypes of IS were classified by Trial of Org 10172 in Acute Stroke Treatment criteria. MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were evaluated using polymerase chain reaction-restriction fragment length polymorphism.
RESULTS
The frequencies of the 5A/6A + 5A/5A genotypes and 5A allele were significantly higher in patients with IS than in controls (P <.001, P <.001, respectively). No association was found between MMP-1 1G/2G polymorphism and overall IS. In subgroup analyses, MMP-1 1G/2G and 2G/2G genotypes increased the risk of small-artery occlusion (SAO) subtype (multivariate-adjusted, P <.001, P = .002, respectively), and MMP-3 5A/6A + 5A/5A genotypes were related with large-artery atherosclerosis (LAA) subtype (multivariate-adjusted, P <.001). Haplotype analyses indicated that 2G-6A and 1G-5A increased the risk of SAO (multivariate-adjusted, P = .029) and LAA (multivariate-adjusted, P <.001), respectively.
CONCLUSIONS
MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms may contribute to different subtypes of IS susceptibility.
背景
基质金属蛋白酶（MMPs）基因的遗传变异可能在缺血性卒中（IS）的发病机制中起重要作用。在此，我们研究汉族人群中MMP-1 -1607 1G/2G和MMP-3 -1171 5A/6A基因多态性与IS病因亚型之间的关联。
方法
共纳入640例符合条件的IS患者和637例年龄及性别匹配的明显健康志愿者。IS亚型根据急性卒中治疗中Org 10172试验标准进行分类。使用聚合酶链反应-限制性片段长度多态性评估MMP-1（-1607 1G/2G）和MMP-3（-1171 5A/6A）多态性。
结果
IS患者中5A/6A + 5A/5A基因型和5A等位基因的频率显著高于对照组（分别为P <.001，P <.001）。未发现MMP-1 1G/2G多态性与总体IS之间存在关联。在亚组分析中，MMP-1 1G/2G和2G/2G基因型增加了小动脉闭塞（SAO）亚型的风险（多因素调整后，分别为P <.001，P =.002），而MMP-3 5A/6A + 5A/5A基因型与大动脉粥样硬化（LAA）亚型相关（多因素调整后，P <.001）。单倍型分析表明，2G-6A和1G-5A分别增加了SAO（多因素调整后，P =.029）和LAA（多因素调整后，P <.001）的风险。
结论
MMP-1（-1607 1G/2G）和MMP-3（-1171 5A/6A）多态性可能导致IS易感性的不同亚型。
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