Ma Ai-jun, Fan Ling-yan, Li Wen-jian, Zhao Hong-qin, Han Ying, Jiang Xue-song, Yi Peng, Li Cui-ling, Song Shuang, Ma Cui-ling, Yao Ru-yong, Pan Xu-dong
Department of Neurology, Affiliated Hospital, Qingdao University Medical College, Qingdao, Shandong 266000, P.R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2013 Aug;30(4):461-6. doi: 10.3760/cma.j.issn.1003-9406.2013.04.018.
To assess the association between matrix metalloproteinase-3 (MM-3) gene polymorphisms and subtypes of ischemic stroke (IS) in northern Han Chinese population.
A total of 289 patients with acute IS (within 3 days after the onset, including 185 with large artery atherosclerosis (LAA) and 104 for small artery occlusion (SAO)) and 175 matched healthy controls were recruited for this case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequenc-based typing (SBT) was carried out to analyze 3 SNPs of the MMP-3 gene.
An incomplete linkage disequilibrium (LD) block was constructed with the 3 SNPs, and the distribution of genotypes of the 3 SNPs differed between the LAA group and controls in a dominant model: Carriers of 5A allele (5A5A+5A6A) of the rs3025058 locus were 1.72 times more susceptible to LAA stroke compared with carriers of 6A6A alleles (P=0.017, OR=1.72, 95% CI: 1.10-2.69), carriers of G alleles (GG+AG) of the rs522616 locus were 0.52 times more susceptible to LAA stroke compared with carriers of AA alleles (P=0.005, OR=0.52, 95% CI: 0.33-0.82), whilst carriers of A allele of the rs679620 locus were 1.55 times more susceptible to LAA stroke compared with carriers of GG alleles (P=0.042, OR=1.55, 95% CI: 1.01-2.37). However, no significant difference has been found between particular genotypes of such SNPs between SAO patients and controls (P> 0.05). Furthermore, 5A-A-A and 6A-A-A haplotypes were significantly more common in LAA group than the controls (P< 0.05), whilst 6A-G-G haplotype has been the opposite (P< 0.01).
Our study has demonstrated that serum MMP-3 level is significantly increased at acute stage of LAA as well as SAO type strokes. There may be an association of rs3025058, rs522616 and rs679620 of MMP-3 gene with susceptibility to LAA stoke in northern Han Chinese population.
评估基质金属蛋白酶-3(MM-3)基因多态性与中国北方汉族人群缺血性脑卒中(IS)亚型之间的关联。
本病例对照研究共纳入289例急性IS患者(发病后3天内,包括185例大动脉粥样硬化型(LAA)和104例小动脉闭塞型(SAO))以及175例匹配的健康对照。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)或序列分型(SBT)方法分析MMP-3基因的3个单核苷酸多态性(SNP)。
构建了包含这3个SNP的不完全连锁不平衡(LD)模块,在显性模型中,LAA组与对照组之间这3个SNP的基因型分布存在差异:rs3025058位点5A等位基因(5A5A+5A6A)携带者发生LAA型脑卒中的易感性是6A6A等位基因携带者的1.72倍(P=0.017,OR=1.72,95%CI:1.10-2.69);rs522616位点G等位基因(GG+AG)携带者发生LAA型脑卒中的易感性是AA等位基因携带者的0.52倍(P=0.005,OR=0.52,95%CI:0.33-0.82);而rs679620位点A等位基因携带者发生LAA型脑卒中的易感性是GG等位基因携带者的1.55倍(P=0.042,OR=1.55,95%CI:1.01-2.37)。然而,SAO患者与对照组之间这些SNP的特定基因型无显著差异(P>0.05)。此外,5A-A-A和6A-A-A单倍型在LAA组中显著高于对照组(P<0.05),而6A-G-G单倍型则相反(P<0.01)。
我们的研究表明,LAA型和SAO型脑卒中急性期血清MMP-3水平均显著升高。MMP-3基因的rs3025058、rs522616和rs679620可能与中国北方汉族人群LAA型脑卒中的易感性相关。