MMP-2 C735T、MMP-9 C1562T基因多态性与缺血性卒中患者的卒中及其亚型大动脉粥样硬化性卒中有关，但与转归无关

目的探讨基质金属蛋白酶（matrix metalloproteinase，MMP）-2C735T和MMP-9C1562T基因多态性与缺血性卒中患者的TOAST分型和转归的关系。方法232例缺血性卒中患者根据TOAST标准分被为大动脉粥样硬化性卒中（large artery atherosclerosis，LAA）（n=37）、心源性脑栓塞（cardioembolism,CE）（n=31）、小动脉闭塞性卒中（small artery occlusion，SAO）（n=65）、其他明确原因导致的卒中（stroke of other demonstrated etiology，SOE）（n=2）和原因不明性卒中（stroke of undemonstrated etiology，SUE）（n=97）；对照组为235名健康者。采用限制性片段长度多态性技术检测MMP-2基因C735T和MMP-9基因C1562T多态性。采用Barthel指数（Barthel Index,BI）评价缺血性卒中患者发病21d和90d时的转归。结果缺血性卒中组（CC基因型：63．36％对54．04％，χ2=4．182，P=0．014；C等位基因：79．31％对74．04％，χ2=3．936；P=0．047）及其LAA亚型（CC基因型：78．37％对54．04％,χ2＝7．740，P=0．005；C等位基因：87．83％对74．04％,χ2=6．655，P=0．01）MMP-2735CC基因型和C等位基因频率均显著高于对照组；缺血性卒中组（CT＋TT基因型：21．98％对13．19％，χ2=6．233，P=0．013；T等位基因：11．64％对7．02％，χ2=5．891，P=0．015）及其LAA亚型（cT＋TT基因型：32．43％对13．19％，χ2=8．892，P=0．003；T等位基因：20．27％对13．19％，χ2=13．950，P=0．000）MMP-91562CT＋TT基因型频率和T等位基因频率也均显著高于对照组。多变量logistic回归分析显示，MMP-2735CC基因型（缺血性卒中：优势比1．099，95％可信区间1．038～1．260，P=0．028；LAA：优势比1．360，95％可信区间1．167～5．774，P=0．009）和MMP-91562TT基因型（缺血性卒中：优势比9．409，95％可信区间1．154—76．722，P=0．036；LAA：优势比8．962，95％可信区间1．380～58．218，P=0．022）携带者缺血性卒中以及LAA亚型发病风险显著增高。MMP-2和MMP-9不同基因型与卒中预后无显著相关性（P均〉0．05）。结论MMP-2735CC基因型和MMP-91562TT基因型与卒中及其LAA亚型的发病风险有关，但与其转归无关。

Polylnorphismsof matrix metalloproteinase-2 C735T and -9 C1562T are associated with stroke and its subtype large artery atherosclerotic stroke,but not associated with the prognosis in patients with ischemic stroke

Objective To investigate the association between matrix metalloproteinase （MMP） -2 C735T and MMP-9 C1562T polymorphisms and TOAST subtypes, the outcome in patients with stroke. Methods A total of 232 patients with ischemic stroke were divided into large artery atherosclerosis （LAA, n =37）, cardioembolism （CE, n =31）, small artery Occlusion （SAO, n = 65） stroke, stroke of other demonstrated etiology （SOE, n = 2）, and stroke of undemonstrated etiology （SUE, n =97） according to TOAST criteria. A total of 235 healthy subjects in the outpatient served as control. Genetic polymorphisms of MMP-2 C735T and MMP-9 C1562T were identified by polymerase chain reaction-restriction fragnent length polymorphism. The outcome of patients was evaluated with Barthel Index （BI） at day 21 and 90 after stroke. Results The frequencies of MMP-2 735CC genotype and C allele in the ischemic stroke group （CC genotype： 63.36% vs. 54. 04%,χ2 =4. 182, P=0. 014; C allele： 79. 31%vs. 74. 04%, χ2 = 3. 936, P = 0. 047 ） and its LAA subtype （ CC genotype： 78.37% vs. 54. 04%, χ2 = 7. 740, P =0. 005; C allele： 87. 83% vs. 74. 04%, χ2 = 6. 655, P = 0. 01 ） were significantly higher than those in the control group. The frequencies of MMP-9 1562CT ＋ TT genotype and T allele in the ischemic stroke group （CT ＋TT genotypes： 21.98% vs. 13.19%,χ2 =6. 233, P = 0. 013; T allele： 11.64% vs. 7. 02%,X2 =5. 891, P=0. 015） and its LAA subtype（CT ＋TT genotypes： 32.43% vs. 13.19% ,χ2 =8. 892, P =0. 003; T allele： 20. 27% vs. 13.19% ,χ2 = 13. 950, P = 0. 000）. Multivariate logistic regression analysis indicated that risk of ischemic stroke and its LAA subtype with MMP-2 735CC genotype （ischemic stroke： odds ratio OR] 1. 099, 95% confidence interval CI] 1. 038-1. 260, P = 0. 028; LAA： OR 1. 360, 95% CI 1. 167-5. 774, P = 0. 009） and with MMP-9 1562TT genotype （ischemic stroke： OR 9. 409, 95% CI 1. 154-76. 722, P = 0. 036; LAA： OR 8. 962, 95% CI 1. 380-58. 218, P = 0. 022） increased significantly. There were no significant correlation between the different ~otypes of MMP-2 and MMP-9 and the outcome of ischemic stroke. Conclusions Polymorphisms of MMP-2 C735T and -9 C1562Tare associated with ischemic stroke and its subtype large artery atherosclerotic stroke, but not associated with the outcome in patients with ischemic stroke