MMP-14基因外显子区单核苷酸多态性与脑梗死的相关性  

Association of MMP-14 gene polymorphism with cerebral infarction - A case-control study

作　　者：李彩[1] 金笑平[1] 朱敏[2] 王凤[1] 胡晓飞[1] 王皖芬[1] 李卫玲[1] 朱峰[1] 郑周[1] 吕海燕[2] 朱宗亚[1] 

机构地区：[1]浙江省台州医院神经内科,317000 [2]浙江省台州医院实验室

出　　处：《中华医学遗传学杂志》2014年第4期491-495,共5页Chinese Journal of Medical Genetics

基　　金：浙江省自然科学基金项目（Y13H293007）;浙江省中医药科学研究基金计划A类（2011ZA111）;台州市科技计划A类（111KY0603）

摘　　要：目的探讨汉族人群基质金属蛋白酶-14（matrix metalloproteinase-14，MMP-14）基因外显子区单核苷酸多态性（single nucleotide polymorphism，SNP）与大动脉粥样硬化型脑梗死的相关性。方法应用酶联免疫吸附法测定574例大动脉粥样硬化型脑梗死患者和463名健康对照者的血清MMP-14水平，应用TaqMan探针法确定MMP-14基因rs1042704和rs2236307两个SNP位点的基因型。多因素Logistic回归分析脑梗死和MMP-14基因多态性及其他脑梗死危险因素的关系。结果MMP-14基因rs1042704位点基因型（χ2=0．593，P=0．441，1-β=0．195）和等位基因频率（χ2=0．580，P=0．447，1-β=0．192）分布在两组间是否有差异尚不能做出可靠结论。MMP-14基因rs2236307位点CT基因型（CT vs.TT，OR=0．705，95％CI：0．536～0．927，P=0．012）、CC基因型（CC vs．TT，OR=0．606，95％CI：0．420～0．873，P=0．007）在脑梗死组中的分布频率偏低。MMP-14基因rs2236307位点C等位基因频率在脑梗死组为37．46％，对照组为43．95％，两者比较差异具有统计学意义（χ2=8．986，P=0．003）。MMP-14血清水平在脑梗死组和对照组间差异有统计学意义（P=0．003），在MMP-14 rs2236307TT基因型群体高于CT、CC基因型群体，差异有统计学意义（P=0．000；P=0．009）。多因素Logistic回归分析显示MMP-14 rs2236307CT＋CC基因型是脑梗死的保护因子（校正OR值为0．710）。结论MMP-14基因rs2236307多态性位点与脑梗死的发病相关，C等位基因可能是脑梗死的保护因子。rs1042704多态性位点与脑梗死无明确关系，其与缺血性脑血管病的关系有待进一步研究。Objective To investigate the association between cerebral infarction （CI） and single nucleotide polymorphism （SNP） in the exon of membrane-type 1 matrix metalloproteinase （MMP-14）gene in Chinese Han population. Methods Five hundred seventy four patients with CI and 463 healthy individuals were recruited. Serum MMP-14 level was measured with enzyme-linked immunosorbent assay （ELISA）. rs1042704 and rs2236307 polymorphisms of the MMP-14 gene were genotyped with a TaqMan assay. Multivariate logistic regression was carried out to analyze the risk factors of CI. Results A significant lower risk of CI was found in individuals with MMP-14 rs2236307 TC and CC genotypes （vs. TT genotype： P〈 0.05）. The frequencies of MMP-14 rs2236307 C allele were significantly different between the CI group （37.46%） and the control group （43.95%） （P=0. 003）. Serum level of MMP-14 was higher in the CI group （P=0. 003） and was also higher in the group with MMP-14 rs2236307 TT genotype compared with those with CT and CC genotypes （P= 0. 000; P=0. 009）. Logistic regression analysis indicated that the MMP-14 rs2236307 CT＋CC genotypes was a protective factor, and that history of hypertension, smoking status, triglycerides, diastolic blood pressure and systolic blood pressure were the independent risk factors of CI （AOR：2. 027, 1. 302, 1. 296, 1. 434, 2. 087; P〈0.05）. Conclusion The rs2236307 polymorphism of MMP-14 gene is associated with CI, for which the C allele maybe a protective factor. No association of MMP-14 gene rs1042704 polymorphism with CI has been found.

关 键 词：脑梗死 基质金属蛋白酶-14基因 单核苷酸多态性 

分 类 号：R743.33[医药卫生—神经病学与精神病学]