基质金属蛋白酶3-1612 基因多态性与 急性缺血性脑卒中的关系

Study on relationship between MMP3-1612 polymorphism and acute ischemic stroke

摘要:

目的 探讨基质金属蛋白酶3（MMP-3）启动子-1612（5A/6A）基因多态性与急性缺血性脑卒中 （AIS）的关系，并进一步探讨其作用机制。方法 采用SNaPshot 微测序技术，检测300 例急性缺血性脑卒中患者 和300 例健康对照者MMP-3 基因-1612（5A/6A）基因型和等位基因频率差异是否存在统计学意义，并且根 据TOAST 分型将AIS 组分为大动脉粥样硬化型（LAA）、小动脉闭塞型（SAO）、心源性栓塞型（CE）、其他 明确病因型（SODE）及其他不明原因型（SUE）亚组，探讨各亚组MMP-3 基因-1612（5A/6A）基因型和等 位基因频率差异是否存在统计学意义。结果 ①携带MMP -3-1612 的5A/5A 基因型数目在AIS 组较对照组增加 （P <0.05）。② MMP-3 启动子区的5A/5A 基因型数目在LAA 型脑梗死增加（P <0.05）。多因素Logistic 回归分 析结果显示：在调整传统危险因素后，MMP-3 启动子区的-1612（5A/6A）基因多态性可增加脑梗死的发病风险。 结论 AIS 组MMP-3 启动子区-1612 基因多态性与急性缺血性脑卒中相关，5A/5A 基因型可能是急性缺血性 脑卒中遗传性危险因素，其作用机制可能与动脉粥样硬化相关，但因本实验样本有限，仍需大样本研究证实。

Abstract:

Objective To investigate the association between 1612 (5A/6A) polymorphism of MMP3 gene and acute ischemic stroke (AIS). Methods SNaP shot minisequencing was used to study whether there was a significant difference in MMP3-1612 genotype and allele frequency between 300 AIS patients and 300 healthy controls. The AIS cases were divided into five subtypes: large-artery atherosclerosis (LAA), small-artery occlusion (SAO), cardioembolism (CE), stroke of other determined etiology (SODE) and stroke of other undetermined etiology (SUE). The differences in MMP3-1612 genotype and allele frequency were studied among the five subtypes. Results For the MMP3 gene-1612 (5A/6A) polymorphism, 5A/5A genotype was significantly increased in the AIS group as compared to the control group (P < 0.05). 5A/5A genotype of MMP3 promoter was significantly increased in the LAA subtype of AIS (P < 0.05). Multiple stepwise logistic regression analysis showed that the 1612-5A/6A polymorphism of MMP3 gene was significantly associated with AIS after adjustion of the conventional risk factors. Conclusions The 1612 polymorphism of MMP3 gene is associated with acute ischemic stroke, the 5A/5A genotype may be the risk factor of acute ischemic stroke. The mechanism may be related to arteriosclerosis. But large samples will be studied to confirm our conclusion.