中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (3): 506-512.doi: 10.4103/1673-5374.245472

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

中国北方汉族人群G蛋白偶联嘌呤能受体P2Y2(P2RY2)与缺血性脑卒中的关系

  

  • 出版日期:2019-03-15 发布日期:2019-03-15
  • 基金资助:

    国家自然科学基金(81070913)

Association of G-protein coupled purinergic receptor P2Y2 with ischemic stroke in a Han Chinese population of North China

Li-Ying Yuan, Zhi-Yi He , Lei Li, Yan-Zhe Wang   

  1. Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2019-03-15 Published:2019-03-15
  • Contact: Zhi-Yi He, PhD, MD, hezhiyi0301@sina.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81070913 (to ZYH).

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摘要：

G蛋白偶联嘌呤能受体P2Y2 (P2RY2)在动脉粥样硬化的机制中起着重要作用，是否也与缺血性卒中密切相关？为评估中国北方汉族人群中P2RY2基因多态性与缺血性卒中风险的关系，试验设计了回顾性病例-对照研究，并共收集了缺血性卒中患者378例和对照组344例的临床资料和外周静脉血标本。缺血性卒中患者来自中国医科大学附属第一医院和辽宁医学院附属第一医院，对照组人群来自中国医科大学体检中心的健康者。根据急性卒中TOAST分型标准，将缺血性卒中患者分为2组：大动脉粥样硬化(LAA)组178例，小动脉闭塞(SAO)组200例。所有受试者检测外周静脉血P2RY2基因(rs4944831, rs1783596和rs4944832)中3个单核苷酸多态性(SNPs)的基因型。rs4944832显性表型(GG vs. GA+AA)在SAO患者与对照组之间的分布差异有显著性意义(OR=1.720，95%CI：1.203-2.458，P < 0.01)。多因素Logistic回归分析显示，在SAO患者中，rs4944832的GG基因型明显高于对照组(OR=1.807，95% CI：1.215-2.687，P < 0.01)。rs4944831-rs1783596-rs4944832组建的单倍型在缺血性卒中患者和对照组中总体分布差异有显著性意义(P < 0.01)。缺血性卒中患者的G-C-G单倍型频率明显高于对照组(P = 0.028)，而T-C-A单倍型频率低于对照组(P = 0.047)。这些结果表明，P2RY2的G-C-G单倍型是缺血性卒中的易感性单倍型，rs4944832的GG基因型可能与中国北方汉族人群SAO的发病有关。实验经中国医科大学第一附属医院伦理委员会（February 20, 2012 (NO.2012-38-1)）和辽宁医科大学第一附属医院的伦理委员会批准（March 1, 2013 (NO.2013-03-1)），受试者均知情同意。方案已经英国临床试验注册中心注册（注册号：ISRCTN11439124，注册日期：2018-08-24），方案版本号1.0。

orcid: 0000-0002-0995-0294(Zhi-Yi He)

关键词: P2RY2基因, 缺血性脑卒中, 单核苷酸多态性, 病例对照研究, 单倍型, 北方汉族人群, 大动脉粥样硬化, 小动脉闭塞, 高血压, 候选基因

Abstract:

The G-protein-coupled purinergic receptor P2Y2 (P2RY2) plays an important role in the mechanism of atherosclerosis, which is relevant to ischemic stroke. This retrospective case-control study aimed to assess the relationship between P2RY2 gene polymorphisms and ischemic stroke risk in the northern Han Chinese population. In this study, clinical data and peripheral blood specimens were collected from 378 ischemic stroke patients and 344 controls. The ischemic stroke participants were recruited from the First Affiliated Hospital of China Med¬ical University and the First Affiliated Hospital of Liaoning Medical University. The controls were recruited from the Health Check Center at the First Affiliated Hospital of China Medical University. Ischemic stroke patients were divided into two subgroups according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification: large-artery atherosclerosis (n = 178) and small-artery occlusion (n = 200) strokes. All subjects were genotyped for three single nucleotide polymorphisms (rs4944831, rs1783596, and rs4944832) in the P2RY2 gene using peripheral venous blood samples. The distribution of the dominant rs4944832 phenotype (GG vs. GA+AA) differed significantly between small-artery occlusion patients and control subjects (odds ratio (OR) = 1.720, 95% confidence interval (CI): 1.203–2.458, P < 0.01). Multivariable logistic regression analysis revealed that the GG genotype of rs4944832 was significantly more prevalent in small-artery oc¬clusion patients than in control subjects (OR = 1.807, 95% CI: 1.215–2.687, P < 0.01). The overall distribution of the haplotype established by rs4944831-rs1783596-rs4944832 was significantly different between ischemic stroke patients and controls (P < 0.01). In ischemic stroke patients, the frequency of the G-C-G haplotype was significantly higher than in control subjects (P = 0.028), whereas the frequency of the T-C-A haplotype was lower than in control subjects (P = 0.047). These results indicate that the G-C-G haplotype of P2RY2 is a suscepti¬bility haplotype for ischemic stroke. In addition, the GG genotype of rs4944832 may be associated with the development of small-artery occlusion in the northern Han Chinese population. The study protocol was approved by the Ethics Committee of the First Affiliated Hos-pital of China Medical University on February 20, 2012 (No. 2012-38-1) and the First Affiliated Hospital of Liaoning Medical University, China, on March 1, 2013 (No. 2013-03-1). All participants gave their informed consent. This trial was registered with the ISRCTN Registry (ISRCTN11439124) on October 24, 2018. Protocol version (1.0).

Key words: nerve regeneration, P2RY2 gene, ischemic stroke, single nucleotide polymorphism, case-control study, haplotype, northern Han Chinese population, large-artery atherosclerosis, small-artery occlusion, hypertension, candidate gene, neural regeneration