中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (3): 463-469.doi: 10.4103/1673-5374.228729

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

血栓素A合酶1基因多态性与中国北方汉族人群发生缺血性卒中风险的关联

  

  • 收稿日期:2017-11-22 出版日期:2018-03-15 发布日期:2018-03-15
  • 基金资助:

    国家自然科学基金（81070913）

Associations between thromboxane A synthase 1 gene polymorphisms and the risk of ischemic stroke in a Chinese Han population

Lei Li, Zhi-yi He, Yan-zhe Wang, Xu Liu, Li-ying Yuan   

  1. Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Received:2017-11-22 Online:2018-03-15 Published:2018-03-15
  • Contact: Zhi-yi He, Ph.D., M.D.,hezhiyi0301@sina.com.
  • Supported by:

    This study was supported by a grant from the National Natural Science Foundation of China, No. 81070913

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摘要：

血栓素A合酶1 (TBXAS1)是合成血栓素A2的关键酶，血栓素A2在缺血性脑卒中发病中发挥重要作用。因此，试验选择了参与动脉粥样硬化形成的TBXAS1基因作为候选基因，采用病例-对照研究的方法，收集370例中国北方汉族人群缺血性脑卒中患者和340例健康对照者外周血样本和临床资料，试验方案在XXX数据库注册，注册号XXX。试验应用单碱基延伸方法检测TBXAS1基因rs2267682及rs10487667位点的多态性，从而探讨TBXAS1基因多态性与中国北方汉族人群缺血性脑卒中的关联。发现TBXAS1基因rs2267682位点的TT基因型和T等位基因频率明显高于对照组(P < 0.01，P =0.02)；携带TT基因型的个体发生缺血性脑卒中的危险是GG+GT基因型的1.8倍(OR=1.80，95%CI：1.16-2.79；P < 0.01)，校正各种混杂因素后发病危险度为1.94倍(OR=1.94，95%CI：1.13-3.33，P =0.02)。由TBXAS1基因rs2267682及rs10487667组建单体型进行单倍型分析结果显示，TG单倍型在缺血性脑卒中组中的分布频率明显高于对照组(OR=1.49，95%CI：1.10-2.00，P < 0.01)。上述数据证实，TBXAS1基因rs2267682位点多态性与中国北方汉族人群缺血性脑卒中的发病相关，rs2267682位点TT基因型和T等位基因可能增加此人群患病风险。

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

 

关键词: 神经再生, 脑损伤, 缺血性脑卒中, 血栓素合成酶1, 单核苷酸多态性, 病例-对照研究, 血栓素A2, 汉族, 单倍型, 大动脉粥样硬化, 小动脉闭塞

Abstract:

Thromboxane A synthase 1 (TBXAS1) catalyses the synthesis of thromboxane A2 (TXA2), which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls (P < 0.01 and P = 0.02). Furthermore, compared with the GG + GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.16–2.79, P < 0.01). Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke (OR = 1.94,95% CI : 1.13–3.33, P = 0.02). The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis (OR = 1.49, 95% CI: 1.10–2.00, P < 0.01). These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559).

Key words: nerve regeneration, brain injury, ischemic stroke, thromboxane A synthase 1, single nucleotide polymorphism, case-control study, thromboxane A2, Chinese Han population, haplotype, large-artery atherosclerosis, small-artery occlusion, neural regeneration