CAJ | 학술논문

目的探讨基质金属蛋白酶（matrix metallop roteinase，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 arery 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Barhel指数（Barthel Index,BI）评价缺血性卒中患者发病21 d和90d时的转归。结果缺血性卒中组（CC基因型：63.36％对54.04％x2=4.182，P=0.014;C等位基因：79.31％对74.04％，x2=3.936,P=0.047）及其LAA亚型（CC基因型：78.37％对54.04％,x2=7.740，P=0.005；C等位基因：87.83％对74.04％,x2 =6.655,P=0.01)MMP-2 735CC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％,x2=6.233,P=0.013;T等位基因：11.64％对7.02％，x2=5.891,P=0.015）及其LAA亚型(CT+TT基因型：32.43％对13.19％，x2=8.892，P=0.003;T等位基因：20.27％对13.19％，x2=13.950，P=0.000) MMP-9 1562CT +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-2 735CC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-9 1562TT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-2 735CC基因型和MMP-9 1562TT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。目的探討基質金屬蛋白酶（matrix metallop roteinase，MMP）-2C735T和MMP-9C1562T基因多態性與缺血性卒中患者的TOAST分型和轉歸的關繫。方法232例缺血性卒中患者根據TOAST標準分被為大動脈粥樣硬化性卒中（large arery atherosclerosis，LAA）(n=37)、心源性腦栓塞(cardioembolism,CE)(n=31)、小動脈閉塞性卒中（small artery occlusion，SAO）(n=65)、其他明確原因導緻的卒中(stroke of other demonstrated etiology，SOE)(n=2)和原因不明性卒中(stroke of undemonstrated etiology，SUE)(n =97)；對照組為235名健康者。採用限製性片段長度多態性技術檢測MMP-2基因C735T和MMP-9基因C1562T多態性。採用Barhel指數（Barthel Index,BI）評價缺血性卒中患者髮病21 d和90d時的轉歸。結果缺血性卒中組（CC基因型：63.36％對54.04％x2=4.182，P=0.014;C等位基因：79.31％對74.04％，x2=3.936,P=0.047）及其LAA亞型（CC基因型：78.37％對54.04％,x2=7.740，P=0.005；C等位基因：87.83％對74.04％,x2 =6.655,P=0.01)MMP-2 735CC基因型和C等位基因頻率均顯著高于對照組；缺血性卒中組（CT+TT基因型：21.98％對13.19％,x2=6.233,P=0.013;T等位基因：11.64％對7.02％，x2=5.891,P=0.015）及其LAA亞型(CT+TT基因型：32.43％對13.19％，x2=8.892，P=0.003;T等位基因：20.27％對13.19％，x2=13.950，P=0.000) MMP-9 1562CT +TT基因型頻率和T等位基因頻率也均顯著高于對照組。多變量logistic迴歸分析顯示，MMP-2 735CC基因型（缺血性卒中：優勢比1.099，95％可信區間1.038～1.260，P=0.028；LAA:優勢比1.360，95％可信區間1.167～5.774,P=0.009）和MMP-9 1562TT基因型（缺血性卒中：優勢比9.409，95％可信區間1.154～76.722,P=0.036；LAA:優勢比8.962，95％可信區間1.380～58.218，P=0.022）攜帶者缺血性卒中以及LAA亞型髮病風險顯著增高。MMP-2和MMP-9不同基因型與卒中預後無顯著相關性（P均＞0.05）。結論 MMP-2 735CC基因型和MMP-9 1562TT基因型與卒中及其LAA亞型的髮病風險有關，但與其轉歸無關。
목적 탐토기질금속단백매（matrix metallop roteinase，MMP）-2C735T화MMP-9C1562T기인다태성여결혈성졸중환자적TOAST분형화전귀적관계。방법232례결혈성졸중환자근거TOAST표준분피위대동맥죽양경화성졸중（large arery atherosclerosis，LAA）(n=37)、심원성뇌전새(cardioembolism,CE)(n=31)、소동맥폐새성졸중（small artery occlusion，SAO）(n=65)、기타명학원인도치적졸중(stroke of other demonstrated etiology，SOE)(n=2)화원인불명성졸중(stroke of undemonstrated etiology，SUE)(n =97)；대조조위235명건강자。채용한제성편단장도다태성기술검측MMP-2기인C735T화MMP-9기인C1562T다태성。채용Barhel지수（Barthel Index,BI）평개결혈성졸중환자발병21 d화90d시적전귀。결과 결혈성졸중조（CC기인형：63.36％대54.04％x2=4.182，P=0.014;C등위기인：79.31％대74.04％，x2=3.936,P=0.047）급기LAA아형（CC기인형：78.37％대54.04％,x2=7.740，P=0.005；C등위기인：87.83％대74.04％,x2 =6.655,P=0.01)MMP-2 735CC기인형화C등위기인빈솔균현저고우대조조；결혈성졸중조（CT+TT기인형：21.98％대13.19％,x2=6.233,P=0.013;T등위기인：11.64％대7.02％，x2=5.891,P=0.015）급기LAA아형(CT+TT기인형：32.43％대13.19％，x2=8.892，P=0.003;T등위기인：20.27％대13.19％，x2=13.950，P=0.000) MMP-9 1562CT +TT기인형빈솔화T등위기인빈솔야균현저고우대조조。다변량logistic회귀분석현시，MMP-2 735CC기인형（결혈성졸중：우세비1.099，95％가신구간1.038～1.260，P=0.028；LAA:우세비1.360，95％가신구간1.167～5.774,P=0.009）화MMP-9 1562TT기인형（결혈성졸중：우세비9.409，95％가신구간1.154～76.722,P=0.036；LAA:우세비8.962，95％가신구간1.380～58.218，P=0.022）휴대자결혈성졸중이급LAA아형발병풍험현저증고。MMP-2화MMP-9불동기인형여졸중예후무현저상관성（P균＞0.05）。결론 MMP-2 735CC기인형화MMP-9 1562TT기인형여졸중급기LAA아형적발병풍험유관，단여기전귀무관。
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 fragment 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％,x2 =4. 182, P=0.014; C allele: 79.31％vs. 74.04％,x2 =3. 936, P =0. 047 ) and its LAA subtype ( CC genotype: 78. 37％ vs. 54. 04％, x2 =7. 740, P =0. 005; C allele: 87. 83％ vs. 74. 04％, x2 =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％,x2 =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％ ,x2 =8. 892, P =0. 003; T allele: 20. 27％ vs. 13.19％ ,x2 =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 genotypes 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