ITGA2 基因双位点多态性与症状性颅内动脉粥样硬化狭窄支架术后缺血事件复发的关联研究

doi:10.3969/j.issn.1006-7795.2026.03.002

首都医科大学学报

• 从分子机制到临床应用:创新药物新突破 • 上一篇下一篇

ITGA2 基因双位点多态性与症状性颅内动脉粥样硬化狭窄支架术后缺血事件复发的关联研究

董怡文¹,叶佳丹²,程晟¹,杨鸿鸽¹,李泽¹,邸宣¹,娄昕^3*＃,李新刚^1*＃,马宁^4,5*＃

1.首都医科大学附属北京友谊医院药学部，北京 100050; 2.中国医学科学院阜外医院药学部，北京 100037；3.中国人民解放军总医院第一医学中心放射诊断科，北京 100853；4.首都医科大学附属北京天坛医院神经介入科，北京 100070； 5.国家神经系统疾病临床医学研究中心，北京 100070

收稿日期:2026-02-13 修回日期:2026-03-11 出版日期:2026-06-21
通讯作者: 娄昕,李新刚,马宁 E-mail:louxin@301hospital.com.cn; lxg198320022003@163.com; maning_03@hotmail.com
基金资助:
国家自然科学基金项目（82203039），北京市科技计划项目（Z221100007422032），北京市教育委员会科技发展计划项目（KM202210025016）。

Association of ITGA2 dual site variants with recurrent ischemic events in patients undergoing stenting for symptomatic intracranial atherosclerotic stenosis

Dong Yiwen¹, Ye Jiadan², Cheng Sheng¹, Yang Hongge¹, Li Ze¹, Di Xuan¹, Lou Xin^3*＃, Li Xingang^1*＃, Ma Ning^4,5*＃

1.Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; 2.Department of Pharmacy, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China; 3.Department of Radiology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; 4.Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; 5.China National Clinical Research Center for Neurologic Diseases, Beijing 100070, China

Received:2026-02-13 Revised:2026-03-11 Online:2026-06-21
Supported by:
This study was supported by National Natural Science Foundation of China (82203039)， Beijing Science and Technology Planning Project (Z221100007422032)， R&D Program of Beijing Municipal Education Commission (KM202210025016).

摘要/Abstract

摘要： 目的探讨症状性颅内动脉粥样硬化狭窄患者基因多态性与双联抗血小板治疗后缺血性不良事件发生的相关性。方法共纳入195例患者，分为发生缺血性不良事件的病例组32例和未发生事件的对照组163例。对17个基因的20个单核苷酸多态性位点进行基因分型。针对病例组与对照组样本量不均衡问题，采用基于组间比例倒数的频数加权法进行加权Logistic回归分析，通过权重校正病例对照比例差异，提高回归结果的稳定性与可靠性。结果 ITGA2基因rs1126643（C807T）和rs1062535（G873A）多态性与缺血性不良事件发生显著相关。病例组ITGA2 rs1126643位点C等位基因、rs1062535位点G等位基因突变频率显著高于对照组（OR=2.97，95%CI：1.702~5.172，P=0.000 1；OR=3.27，95%CI：1.762~6.066，P=0.000 2），其余基因型组间比较无统计学差异。结论 ITGA2基因C807T和G873A多态性与中国患者术后缺血性事件复发风险升高相关；检测该基因多态性有助于识别缺血事件复发高危患者。

关键词: 颅内动脉粥样硬化性狭窄, 缺血事件, 双联抗血小板治疗, 单核苷酸多态性, 遗传标志物, ITGA2

Abstract: Objective To investigate the correlation between gene polymorphisms and the occurrence of adverse clinical events following dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic stenosis. Methods A total of 195 patients were enrolled and categorized into 32 cases (those with clinical adverse events) and 163 controls (without events). Genotyping of 20 single nucleotide polymorphism (SNP) from 17 genes was executed. To address the imbalance in sample size between cases (n=32) and controls (n=163), weighted Logistic regression analysis was performed using frequency weights based on the reciprocal of group proportions. Weights were calculated to account for the unequal case-control ratio and improve the stability and reliability of regression estimates. Results The ITGA2 rs1126643 (C807T) and rs1062535 (G873A) polymorphisms were significantly correlated with adverse clinical events. Specifically, the mutant frequency of allele C (ITGA2 rs1126643) and allele G (ITGA2 rs1062535) was significantly higher in cases compared to controls (OR=2.97, 95%CI: 1.702-5.172, P=0.000 1; OR=3.27, 95%CI:1.762-6.066, P=0.000 2, respectively). Other genotypes showed no significant differences between the groups. Conclusion The ITGA2 C807T and G873A polymorphisms are associated with an increased risk of recurrent ischemic events in Chinese patients with symptomatic intracranial atherosclerotic stenosis after stenting. Detection of these variants may help identify individuals at high risk of recurrent ischemic events in this specific population.

Key words: intracranial atherosclerotic stenosis, ischemic events, dual antiplatelet therapy, single nucleotide polymorphism, genetic markers, ITGA2

中图分类号:

R743

董怡文, 叶佳丹, 程晟, 杨鸿鸽, 李泽, 邸宣, 娄昕, 李新刚, 马宁. ITGA2 基因双位点多态性与症状性颅内动脉粥样硬化狭窄支架术后缺血事件复发的关联研究[J]. 首都医科大学学报, doi: 10.3969/j.issn.1006-7795.2026.03.002.

Dong Yiwen, Ye Jiadan, Cheng Sheng, Yang Hongge, Li Ze, Di Xuan, Lou Xin, Li Xingang, Ma Ning. Association of ITGA2 dual site variants with recurrent ischemic events in patients undergoing stenting for symptomatic intracranial atherosclerotic stenosis[J]. Journal of Capital Medical University, doi: 10.3969/j.issn.1006-7795.2026.03.002.

参考文献

［1］GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019［J］. Lancet Neurol, 2021, 20(10): 795-820.
［2］Ma Q F, Li R, Wang L J, et al. Temporal trend and attributable risk factors of stroke burden in China, 1990-2019: an analysis for the Global Burden of Disease Study 2019［J］. Lancet Public Health, 2021, 6(12): e897-e906.
［3］Bergmark B A, Mathenge N, Merlini P A, et al. Acute coronary syndromes［J］. Lancet, 2022, 399(10332): 1347-1358.
［4］Xian Y, Xu H L, Matsouaka R, et al. Analysis of prescriptions for dual antiplatelet therapy after acute ischemic stroke［J］. JAMA Netw Open, 2022, 5(7): e2224157.
［5］Simonte G, Guglielmini G, Falcinelli E, et al. High-on-treatment platelet reactivity predicts adverse outcome after carotid artery stenting: a prospective study［J］. Thromb Res, 2023, 222: 117-123.
［6］Shah J, Liu S M, Yu W G. Contemporary antiplatelet therapy for secondary stroke prevention: a narrative review of current literature and guidelines［J］. Stroke Vasc Neurol, 2022, 7(5): 406-414.
［7］Khan H, Kanny O, Syed M H, et al. Aspirin resistance in vascular disease: a review highlighting the critical need for improved point-of-care testing and personalized therapy［J］. Int J Mol Sci, 2022, 23(19):11317.
［8］Patel S, Arya V, Saraf A, et al. Aspirin and clopidogrel resistance in Indian patients with ischemic stroke and its associations with gene polymorphisms: a pilot study［J］. Ann Indian Acad Neurol, 2019, 22(2): 147-152.
［9］Ross S, Krebs K, Pare G, et al. Pharmacogenomics in stroke and cardiovascular disease: state of the art［J］. Stroke, 2023, 54(1): 270-278.
［10］Montinari M R, Minelli S, De Caterina R. The first 3500 years of aspirin history from its roots-a concise summary［J］. Vascul Pharmacol, 2019, 113: 1-8.
［11］Li X Q, Ma N, Li X G, et al. Association of PON1, P2Y12 and COX1 with recurrent ischemic events in patients with extracranial or intracranial stenting［J］. PLoS One, 2016, 11(2): e0148891.
［12］Zhao Z G, Li X G, Sun S S, et al. Impact of genetic polymorphisms related to clopidogrel or acetylsalicylic acid pharmacology on clinical outcome in Chinese patients with symptomatic extracranial or intracranial stenosis［J］. Eur J Clin Pharmacol, 2016, 72(10): 1195-1204.
［13］Pereira N L, Rihal C S, So D, et al. Clopidogrel pharmacogenetics［J］. Circ Cardiovasc Interv, 2019, 12(4): e007811.
［14］Saiz-Rodríguez M, Belmonte C, Caniego J L, et al. Influence of CYP450 enzymes, CES1, PON1, ABCB1, and P2RY12 polymorphisms on clopidogrel response in patients subjected to a percutaneous neurointervention［J］. Clin Ther, 2019, 41(6): 1199-1212.e2.
［15］Pan Y S, Elm J J, Li H, et al. Outcomes associated with clopidogrel-aspirin use in minor stroke or transient ischemic attack: a pooled analysis of clopidogrel in high-risk patients with acute non-disabling cerebrovascular events (CHANCE) and platelet-oriented inhibition in new TIA and minor ischemic stroke (POINT) trials［J］. JAMA Neurol, 2019, 76(12): 1466-1473.
［16］Brown T, Gonzales N. Optimizing choice of dual antiplatelet therapy in CYP2C19 loss-of-function carriers［J］. Neurology, 2023, 100(5): 223-224.
［17］Yip V L M, Pirmohamed M. Expanding role of pharmacogenomics in the management of cardiovascular disorders［J］. Am J Cardiovasc Drugs, 2013, 13(3): 151-162.
［18］Jackson S P. Arterial thrombosis-insidious, unpredictable and deadly［J］. Nat Med, 2011, 17(11): 1423-1436.
［19］Kunicki T J, Orchekowski R, Annis D, et al. Variability of integrin alpha 2 beta 1 activity on human platelets［J］. Blood, 1993, 82(9): 2693-2703.［20］Deckmyn H, Chew S L, Vermylen J. Lack of platelet response to collagen associated with an autoantibody against glycoprotein IA: a novel cause of acquired qualitative platelet dysfunction［J］. Thromb Haemost, 1990, 64: 74-79.
［21］Huang X Y, Fu W J, Mei Z Z, et al. Association between platelet glycoprotein Ia C807T gene polymorphism and ischemic stroke: a meta-analysis in a separate ethnic group［J］. Cell Mol Biol, 2017, 63(11): 111-115.
［22］Liu H, Wang Y, Zheng J, et al. Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: evidence from a comprehensive meta-analysis［J］. Int J Stroke, 2017, 12(1): 46-70.
［23］De Oliveira M H, André C, Spector N, et al. 807C/T polymorphism in the platelet glycoprotein Ia gene in young patients with ischemic stroke of undetermined etiology［J］. Blood Coagul Fibrinolysis, 2007, 18(7): 599-602.
［24］Nikolopoulos G K, Tsantes A E, Bagos P G, et al. Integrin, alpha 2 gene C807T polymorphism and risk of ischemic stroke: a meta-analysis［J］. Thromb Res, 2007, 119(4): 501-510.
［25］Dodson P M, Haynes J, Starczynski J, et al. The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion［J］. Eye, 2003, 17(6): 772-777.
［26］Wu G L, Xi Y J, Yao L, et al. Genetic polymorphism of ITGA2 C807T can increase the risk of ischemic stroke［J］. Int J Neurosci, 2014, 124(11): 841-851.
［27］Lloyd-Jones D, Adams R J, Brown T M, et al. Executive summary: heart disease and stroke statistics—2010 update: a report from the American Heart Association［J］. Circulation, 2010, 121(7): 948-954.
［28］Lewis J P, Ryan K, O'Connell J R, et al. Genetic variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes［J］. Circ Cardiovasc Genet, 2013, 6(2): 184-192.

ITGA2 基因双位点多态性与症状性颅内动脉粥样硬化狭窄支架术后缺血事件复发的关联研究

Association of ITGA2 dual site variants with recurrent ischemic events in patients undergoing stenting for symptomatic intracranial atherosclerotic stenosis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 1

编辑推荐

Metrics

本文评价