血小板活化因子乙酰水解酶基因多态性V279F与缺血性卒中易感性及复发的相关性研究

摘要/Abstract

摘要：

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。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（small-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。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。

文章导读： 本研究分析发现血小板活化因子乙酰水解酶基因多态性V279F与缺血性卒中易感性及复发相关。

关键词: 血小板活化因子乙酰水解酶; 缺血性卒中; 基因多态性; 复发

Abstract:

Objective To evaluate the relationship of platelet-activating factor acetylhydrolase (PAF-AH) gene V279F polymorphisms with susceptibility and recurrence to ischemic stroke (IS). 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) and V279F 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 of V279F with stroke recurrence was analyzed by multivariate survival analysis. 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 of FF+VF genotype (44.6%), VF genotype (28.8%) and F allele (16.5%) of V279F 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 with V279F 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 significantly increased, especially in LAA subtype. The V279F variant in PLA2G7 gene might contribute to susceptibility of LAA subgroup IS and recurrence of IS.

Key words: Platelet-activating factor acetylhydrolase; Ischemic stroke; Single-nucleotide polymorphism; Recurrence

马永盛，潘旭东. 血小板活化因子乙酰水解酶基因多态性V279F与缺血性卒中易感性及复发的相关性研究[J]. 中国卒中杂志, 2015, 10(06): 475-482.

MA Yong-Sheng, PAN Xu-Dong. . Association of Platelet-Activating Factor Acetylhydrolase Gene V279F Polymorphisms with Susceptibility and Recurrence of Ischemic Stroke[J]. Chinese Journal of Stroke, 2015, 10(06): 475-482.

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