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 (8): 1404-1411.doi: 10.4103/1673-5374.253525

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

中国西南地区汉族急性缺血性脑卒中患者与健康人脑源性神经营养因子基因多态性的差异

  

  • 出版日期:2019-08-15 发布日期:2019-08-15
  • 基金资助:

    中国国家自然科学基金项目(81472162)

Differences in brain-derived neurotrophic factor gene polymorphisms between acute ischemic stroke patients and healthy controls in the Han population of southwest China

Jie Zhou , Meng-Meng Ma , Jing-Huan Fang, Lei Zhao, Mu-Ke Zhou, Jian Guo , Li He   

  1. Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
  • Online:2019-08-15 Published:2019-08-15
  • Contact: Jian Guo, MD, jian_guo@scu.edu.cn; Li He, MD, heli2003new@126.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81472162 (to MKZ).

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摘要：

脑源性神经营养因子基因中的单核苷酸多态性可能影响其分泌和功能，继而影响缺血性卒中的发生、严重程度和预后。试验于2011年9月至2014年12月在四川大学华西医院神经内科招募了778例急性期缺血性卒中患者（男475例，女303例，年龄64.0±12.6岁）和865名健康对照者（男438名，女427名，年龄51.7±14.7岁）。在入院后立即使用美国国立卫生研究院卒中量表评估急性期神经功能缺损的严重程度，根据Org 10172急性卒中治疗分类标准将患者分为不同的亚型，在出院时使用改良的Rankin量表评估早期预后。结果显示携带rs7124442中C等位基因的受试者比携带T等位基因者预后不良风险更低（OR = 0.67，95％CI：0.45-1.00，P = 0.048）。CC+TC基因型者比TT者风险更低（OR= 0.65，95％CI：0.42-1.00，P=0.049）。rs6265的AA基因型与大动脉粥样硬化发生有关（OR=0.58，95％CI：0.37-0.90，P=0.015）。提示发现rs7124442中C等位基因和CC+TC基因型可能是缺血性卒中预后的保护因素，rs6265中AA基因型可能是大动脉粥样硬化的保护因素。试验于2008年7月25日经四川大学华西医院伦理委员会批准，批准号2008（4）。

orcid: 0000-0001-5635-8851 (Jian Guo)
           0000-0002-2034-1027 (Li He)

关键词: 缺血性卒中, 脑源性神经营养因子, 单核苷酸多态性, 发病风险, 卒中严重程度, 预后, rs6265, rs7124442, 神经再生

Abstract:

Single-nucleotide polymorphisms in the brain-derived neurotrophic factor gene may affect the secretion and function of brain-derived neurotrophic factor, thereby affecting the occurrence, severity and prognosis of ischemic stroke. This case-control study included 778 pa¬tients (475 males and 303 females, mean age of 64.0 ± 12.6 years) in the acute phase of ischemic stroke and 865 control subjects (438 males and 427 females, mean age of 51.7 ± 14.7 years) from the Department of Neurology, West China Hospital, Sichuan University, China between September 2011 and December 2014. The patients’ severities of neurological deficits in the acute phase were assessed using the National Institutes of Health Stroke Scale immediately after admission to hospital. The ischemic stroke patients were divided into different subtypes according to the Trial of Org 10172 in Acute Stroke Treatment classification. Early prognosis was evaluated using the Modified Rankin Scale when the patients were discharged. Genomic DNA was extracted from peripheral blood of participants. Genotyping of rs7124442 and rs6265 was performed using Kompetitive Allele Specific polymerase chain reaction genotyping technology. Our results demonstrated that patients who carried the C allele of the rs7124442 locus had a lower risk of poor prognosis than the T allele carriers (odds ratio [OR] = 0.67; 95% confidence interval [CI]: 0.45–1.00; P = 0.048). The patients with the CC or TC genotype also exhibited lower risk than TT carriers (OR = 0.65; 95% CI: 0.42–1.00; P = 0.049). The AA genotype at the rs6265 locus was associated with the occurrence of ischemic stroke in patients with large-artery atherosclerosis (OR = 0.58; 95% CI: 0.37–0.90; P = 0.015). We found that the C allele (CC and TC genotypes) at the rs7124442 locus may be protective for the prognosis of ischemic stroke. The AA genotype at the rs6265 locus is likely a protective factor against the occurrence of ischemic stroke in patients with large-artery atherosclerosis. The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval ID number 2008[4], on July 25, 2008.

Key words: nerve regeneration, ischemic stroke, brain-derived neurotrophic factor, single-nucleotide polymorphism, risk, stroke severity, prognosis, rs6265, rs7124442, neural regeneration