[1]胡曼,易兴阳,周强,等.P53凋亡通路基因之间交互作用与急性缺血性脑卒中后神经功能恶化和功能预后的关系[J].卒中与神经疾病杂志,2023,30(01):14-18,41.[doi:10.3969/j.issn.1007-0478.2023.01.003]
　Hu Man*,Yi Xingyang,Zhou Qiang,et al.The correlation between interactionsamong variants of P53 apoptoticpathway genes with neurologic deterioration and functional outcome in patients with acute ischemic stroke[J].Stroke and Nervous Diseases,2023,30(01):14-18,41.[doi:10.3969/j.issn.1007-0478.2023.01.003]
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P53凋亡通路基因之间交互作用与急性缺血性脑卒中后神经功能恶化和功能预后的关系()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第30卷
期数:
2023年01期
页码:
14-18,41
栏目:
论著
出版日期:
2023-03-20

文章信息/Info

Title:
The correlation between interactionsamong variants of P53 apoptoticpathway genes with neurologic deterioration and functional outcome in patients with acute ischemic stroke
文章编号:
1007-0478(2023)01-0014-06
作者:
胡曼; 易兴阳; 周强; 任高平; 林静; 李洁; 王淳
610000 成都中医药大学医学与生命科学学院(胡曼); 四川省德阳市人民医院神经内科[易兴阳(通信作者)任高平 李洁 王淳]; 温州医科大学第三附属医院(周强)
Author(s):
Hu Man*;  Yi Xingyang;  Zhou Qiang;  et al.
*Department of Neurology, Chengdu University of Traditional Chinese Medicine, Chengdu 610000
关键词:
基因多态性 缺血性脑卒中 鼠双微体基因-2 基质金属蛋白酶-9 神经功能恶化 P53 相关性
Keywords:
Genetic polymorphism Ischemic stroke MDM-2 MMP-9 Neurologic deterioration P53 Correlation
分类号:
R743.3
DOI:
10.3969/j.issn.1007-0478.2023.01.003
文献标志码:
A
摘要:
目的 探讨P53凋亡通路基因多态性与缺血性脑卒中(Ischemic stroke,IS)后神经功能恶化(Neurologic deterioration,ND)和功能预后的关系。方法 对急性缺血性脑卒中患者的9个凋亡相关基因位点多态性进行测定,采用广义多因素降维法(Generalized multifactor dimensionality reduction,GMDR)分析基因-基因交互作用; 原发终点为ND; ND定义为急性缺血性脑卒中后10 d内病情恶化,美国国立卫生研究院卒中量表(National institutes of health stroke scale,NIHSS)评分与入院时相比增加2分及以上者; 次要终点为急性缺血性脑卒中后第90 d用改良Rankin量表(Modified rankin scale,mRS)评估的功能预后。结果 纳入705例IS患者,其中174例(24.7%)患者发生ND,184例(26.1%)患者功能预后不良(mRS评分>2)。单因素分析显示,9个基因位点多态性与ND发生和功能预后无相关性,但GMDR分析发现P53 rs1042522、鼠双微体基因-2(Murine double minute-2,MDM-2)rs2279744和基质金属蛋白酶-9(Matrix metalloproteinase-9,MMP-9)rs3918242之间存在基因-基因交互作用,这3个基因位点高风险交互增加了ND发生的风险[危害比(Hazard ratio,HR)=2.04,95%置信区间(Confidence interval,CI)=1.22～5.64,P=0.018]和不良的功能预后[比值比(Odds ratio,OR)=2.68,95% CI=1.68～7.86,P=0.004)。结论 P53 rs1042522,MDM-2 rs2279744,MMP-9 rs3918242交互作用可增加急性IS后ND的发生风险及不良的功能预后,可作为预测急性缺血性脑卒中后ND和不良功能结局的基因标志物。
Abstract:
ObjectiveTo investigate the association of variants in P53 apoptotic pathway genes with Neurologic deterioration(ND)and functional outcome in patients with acute ischemic stroke(AIS).Methods Genotypes of nine variants in apoptosis-relevant genes were measured in patients with AIS. Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction(GMDR). The primary outcome was ND. ND was diagnosed in patients who worsened ≥2 points(National Institutes of Health Stroke Scale. NIHSS score)within the first 10 days of stroke onset. The secondary outcome was functional status at 90 days after AIS as measured by modified Rankin Scale(mRS)score.Results A total of 705 enrolled patients, ND occurred in 174(24.7%)patients, and 184(26.1%)patients were poor functional outcome(mRS score >2). Although the nine variants were not significantly associated with ND and functional outcome by univariate analysis, there was a gene-gene interaction among P53 rs1042522, MDM-2 rs2279744, and MMP-9 rs3918242 using GMDR analysis. The high-risk interaction among the three variants was independently associated with higher risk of ND(HR=2.04, 95% CI=1.22～5.64, P=0.018)and poor functional outcome(OR=2.68, 95% CI=1.68～7.86, P=0.004)after adjusting for the covariates.Conclusion The interactions among P53 rs1042522, MDM-2 rs2279744 and MMP-9 rs3918242 may increase the risk of ND and poor functionaloutcome, and may be considered as a genetic marker of predicting ND and poor functionaloutcome after stroke.

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备注/Memo

备注/Memo:
基金项目:四川省科技厅科学研究基金项目(2018JY0164)); 四川省卫生计划委重点科研项目(16ZD046)
更新日期/Last Update: 2023-03-20