中国卒中杂志
中國卒中雜誌
중국졸중잡지
CHINESE JOURNAL OF STROKE
2015年
6期
475-482
,共8页
血小板活化因子乙酰水解酶%缺血性卒中%基因多态性%复发
血小闆活化因子乙酰水解酶%缺血性卒中%基因多態性%複髮
혈소판활화인자을선수해매%결혈성졸중%기인다태성%복발
Platelet-activating factor acetylhydrolase%Ischemic stroke%Single-nucleotide polymorphism%Recurrence
目的评价血小板活化因子（platelet-activating factor，PAF）乙酰水解酶（acetylhydrolase，AH）基因多态性位点V279F与缺血性卒中易感性及复发的关系。<br> 方法本研究连续选取2008年11月～2014年11月山东省潍坊市人民医院神经内科住院的386首发急性TOAST分型[5]中大动脉粥样硬化（large-artery atherosclerosis，LAA）性卒中和小动脉闭塞（smal-artery occlusion，SAO）性卒中患者共386例为试验组和386例健康体检者，作为对照组，采用酶联免疫吸附法（enzyme linked immunosorbent assay，ELISA）测定血清PAF-AH浓度，聚合酶链反应（polymerase chain reaction，PCR）及基因直接测序法测定V279F基因位点多态性，对缺血性卒中患者平均随访4.5年，通过多元生存分析，探讨基因多态性与缺血性卒中复发的相关性。<br> 结果缺血性卒中患者血清PAF-AH浓度[（4.78±1.28）μg/L]高于对照组[（4.11±1.34）μg/L]， V279F位点中FF+VF基因型频率（44.6%），VF基因型频率（28.8%）和F等位基因频率（16.5%）在缺血性卒中组及LAA性卒中组均高于对照组（30.4%，22.3%，12.2%），差异有显著性（P=0.023，P=0.031， P=0.022）。卒中亚组分析显示V279F多态性与LAA性卒中相关性更强。随访结果提示，25.8%患者缺血性卒中复发，将高血压、糖尿病、高血脂、吸烟史、既往短暂性脑缺血发作病史及基因型分布进行多元回归分析显示，VF+FF基因型与缺血性卒中及LAA性卒中复发相关[风险比（hazard ratio，HR）1.75，95%可信区间（confidence interval，CI）1.03～2.29，P=0.041；HR 1.84，95%CI 1.13～2.41，P=0.037）]。结论缺血性卒中患者Lp-pla2水平升高，LAA性卒中升高最明显；V279F基因多态性可能与LAA性卒中的易感性相关，与缺血性卒中及LAA性卒中复发相关。
目的評價血小闆活化因子（platelet-activating factor，PAF）乙酰水解酶（acetylhydrolase，AH）基因多態性位點V279F與缺血性卒中易感性及複髮的關繫。<br> 方法本研究連續選取2008年11月～2014年11月山東省濰坊市人民醫院神經內科住院的386首髮急性TOAST分型[5]中大動脈粥樣硬化（large-artery atherosclerosis，LAA）性卒中和小動脈閉塞（smal-artery occlusion，SAO）性卒中患者共386例為試驗組和386例健康體檢者，作為對照組，採用酶聯免疫吸附法（enzyme linked immunosorbent assay，ELISA）測定血清PAF-AH濃度，聚閤酶鏈反應（polymerase chain reaction，PCR）及基因直接測序法測定V279F基因位點多態性，對缺血性卒中患者平均隨訪4.5年，通過多元生存分析，探討基因多態性與缺血性卒中複髮的相關性。<br> 結果缺血性卒中患者血清PAF-AH濃度[（4.78±1.28）μg/L]高于對照組[（4.11±1.34）μg/L]， V279F位點中FF+VF基因型頻率（44.6%），VF基因型頻率（28.8%）和F等位基因頻率（16.5%）在缺血性卒中組及LAA性卒中組均高于對照組（30.4%，22.3%，12.2%），差異有顯著性（P=0.023，P=0.031， P=0.022）。卒中亞組分析顯示V279F多態性與LAA性卒中相關性更彊。隨訪結果提示，25.8%患者缺血性卒中複髮，將高血壓、糖尿病、高血脂、吸煙史、既往短暫性腦缺血髮作病史及基因型分佈進行多元迴歸分析顯示，VF+FF基因型與缺血性卒中及LAA性卒中複髮相關[風險比（hazard ratio，HR）1.75，95%可信區間（confidence interval，CI）1.03～2.29，P=0.041；HR 1.84，95%CI 1.13～2.41，P=0.037）]。結論缺血性卒中患者Lp-pla2水平升高，LAA性卒中升高最明顯；V279F基因多態性可能與LAA性卒中的易感性相關，與缺血性卒中及LAA性卒中複髮相關。
목적평개혈소판활화인자（platelet-activating factor，PAF）을선수해매（acetylhydrolase，AH）기인다태성위점V279F여결혈성졸중역감성급복발적관계。<br> 방법본연구련속선취2008년11월～2014년11월산동성유방시인민의원신경내과주원적386수발급성TOAST분형[5]중대동맥죽양경화（large-artery atherosclerosis，LAA）성졸중화소동맥폐새（smal-artery occlusion，SAO）성졸중환자공386례위시험조화386례건강체검자，작위대조조，채용매련면역흡부법（enzyme linked immunosorbent assay，ELISA）측정혈청PAF-AH농도，취합매련반응（polymerase chain reaction，PCR）급기인직접측서법측정V279F기인위점다태성，대결혈성졸중환자평균수방4.5년，통과다원생존분석，탐토기인다태성여결혈성졸중복발적상관성。<br> 결과결혈성졸중환자혈청PAF-AH농도[（4.78±1.28）μg/L]고우대조조[（4.11±1.34）μg/L]， V279F위점중FF+VF기인형빈솔（44.6%），VF기인형빈솔（28.8%）화F등위기인빈솔（16.5%）재결혈성졸중조급LAA성졸중조균고우대조조（30.4%，22.3%，12.2%），차이유현저성（P=0.023，P=0.031， P=0.022）。졸중아조분석현시V279F다태성여LAA성졸중상관성경강。수방결과제시，25.8%환자결혈성졸중복발，장고혈압、당뇨병、고혈지、흡연사、기왕단잠성뇌결혈발작병사급기인형분포진행다원회귀분석현시，VF+FF기인형여결혈성졸중급LAA성졸중복발상관[풍험비（hazard ratio，HR）1.75，95%가신구간（confidence interval，CI）1.03～2.29，P=0.041；HR 1.84，95%CI 1.13～2.41，P=0.037）]。결론결혈성졸중환자Lp-pla2수평승고，LAA성졸중승고최명현；V279F기인다태성가능여LAA성졸중적역감성상관，여결혈성졸중급LAA성졸중복발상관。
Objective To evaluate the relationship of platelet-activating factor acetylhydrolase (PAF-AH) gene V279F polymorphisms with susceptibility and recurrence to ischemic stroke (IS). <br> Methods A total of 386 inpatients with ischemic stroke in Weifang People's Hospital and 386 healthy controls were recruited in the study consecutively from November 2008 to November 2014. Patients were divided into large-artery atherosclerosis (LAA) group and small-artery occlusion (SAO) group acording to the Trial of Org10172 in Acute Stroke Treatment (TOAST). The serum Lp-pla2 level were measured by enzyme linked immunosorbent assay (ELISA). The single nucleotide polymorphisms (SNP) andV279F were analyzed by the polymerase chain reaction (PCR) and sequencing assay was used to detect gene polymorphism. Long-term follow-up (median 4.5 years) was obtained in the patients and the association of SNP ofV279F with stroke recurrence was analyzed by multivariate survival analysis. <br> Results The serum PAF-AH level ([4.78±1.28] μg/L) of the patients of IS group was higher than that in healthy controls ([4.11±1.34] μg/L) (P<0.01). The frequencies ofFF+VF genotype (44.6%), VF genotype (28.8%) andF allele (16.5%) ofV279F in the patients with IS were significantly higher than those in the controls (30.4%, 22.3%, 12.2% respectively), (P=0.023,P=0.031,P=0.022, respectively). Furthermore, subgroup analysis showed that a significant association withV279F was found in LAA subgroup. Recurrence of IS events was fund in 25.8% of the patients from the follow up results. On Cox regression analysis with hypertension, diabetes, hyperlipidemia, history of smoking and transient ischemic attack, gentype,VF+FF genotype predicted the recurrence of IS and LAA subgroup (HR 1.75, 95%CI 1.03~2.29,P=0.041;HR 1.84, 95%CI 1.13~2.41,P=0.037). Conclusion The study indicated that the level of plasma Lp-pla2 in IS patients was signiifcantly increased, especially in LAA subtype. TheV279F variant in PLA2G7 gene might contribute to susceptibility of LAA subgroup IS and recurrence of IS.
