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新型 CD137 基因多态性与中国北方汉族人群缺血性脑卒中易感性的关联

Novel CD137 Gene Polymorphisms and Susceptibility to Ischemic Stroke in the Northern Chinese Han Population.

机构信息

Department of Ultrasound, The 2nd Affiliated Hospital of Harbin Medical University, NO.246, Xuefu Road, Nangang District, Harbin, 150081, Heilongjiang, People's Republic of China.

Department of Pathology, The 1st Hospital of Harbin, NO.151, Diduan Road, Daoli District, Harbin, 150081, Heilongjiang, People's Republic of China.

出版信息

Neuromolecular Med. 2017 Sep;19(2-3):413-422. doi: 10.1007/s12017-017-8457-7. Epub 2017 Jul 28.

DOI:10.1007/s12017-017-8457-7
PMID:28755037
Abstract

Ischemic stroke is a leading cause of mortality and morbidity worldwide, and atherosclerosis is one of the major risk factors for this neurologic deficit. Recent studies have revealed the important role of CD137 in human atherosclerosis. Here, we analyzed the association of CD137 single nucleotide polymorphisms (SNPs) with ischemic stroke. We assessed three SNPs (rs161827, rs161818, and rs161810) of the CD137 gene and their association with ischemic stroke in a northern Chinese Han population. A total of 496 ischemic stroke patients and 486 gender-matched control subjects were genotyped. We classified these patients according to complications with diabetes and hypertension and also by ischemic stroke subtypes. Allele, genotype, and haplotype association studies were tested in all patients and subgroups. We used multivariable logistic regression analysis combined with 10,000 permutations to analyze the association of CD137 polymorphisms with ischemic stroke. After adjusting for relevant factors, rs161827 was significantly different between patients with and without diabetes and the control group (p = 0.0001, p = 0.014, and p = 0.0001, respectively). In addition, rs161818 and rs161810 differed significantly between patients without diabetes and the control subjects (p = 0.0001 and p = 0.004, respectively). rs161827, rs161818, and rs161810 were all statistically significant among the combination stroke subgroup compared with the controls. These results indicate that the CD137 gene is associated with risk of ischemic stroke in the northern Han Chinese. Moreover, CD137 gene polymorphism may be one mediating factor between diabetes and ischemic stroke.

摘要

缺血性脑卒中是全球范围内导致死亡和发病的主要原因之一,而动脉粥样硬化是这种神经功能缺损的主要危险因素之一。最近的研究揭示了 CD137 在人类动脉粥样硬化中的重要作用。在这里,我们分析了 CD137 单核苷酸多态性(SNP)与缺血性脑卒中的关系。我们评估了 CD137 基因的三个 SNP(rs161827、rs161818 和 rs161810)及其与中国北方汉族人群缺血性脑卒中的关系。共对 496 例缺血性脑卒中患者和 486 名性别匹配的对照组进行了基因分型。我们根据是否合并糖尿病和高血压将这些患者进行分类,还根据缺血性脑卒中亚型进行了分类。在所有患者和亚组中进行了等位基因、基因型和单倍型关联研究。我们使用多元逻辑回归分析结合 10000 次置换来分析 CD137 多态性与缺血性脑卒中的关联。在调整相关因素后,rs161827 在合并糖尿病和不合并糖尿病的患者与对照组之间差异有统计学意义(p=0.0001,p=0.014,p=0.0001,分别)。此外,rs161818 和 rs161810 在不合并糖尿病的患者与对照组之间差异有统计学意义(p=0.0001,p=0.004,分别)。与对照组相比,rs161827、rs161818 和 rs161810 在组合脑卒中亚组中均有统计学意义。这些结果表明,CD137 基因与中国北方汉族人群缺血性脑卒中的风险相关。此外,CD137 基因多态性可能是糖尿病与缺血性脑卒中之间的一个中介因素。

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本文引用的文献

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KALRN Rare and Common Variants and Susceptibility to Ischemic Stroke in Chinese Han Population.KALRN基因罕见和常见变异与中国汉族人群缺血性脑卒中易感性
Neuromolecular Med. 2015 Sep;17(3):241-50. doi: 10.1007/s12017-015-8352-z. Epub 2015 Apr 28.
2
CD137-inducing factors from T cells and macrophages accelerate the destabilization of atherosclerotic plaques in hyperlipidemic mice.来自T细胞和巨噬细胞的CD137诱导因子加速高脂血症小鼠动脉粥样硬化斑块的不稳定。
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Human genetic evidence for involvement of CD137 in atherosclerosis.
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Mol Med. 2014 Oct 14;20(1):456-65. doi: 10.2119/molmed.2014.00004.
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An association study on renalase polymorphisms and ischemic stroke in a Chinese population.肾酶多态性与中国人群缺血性脑卒中的关联研究。
Neuromolecular Med. 2013 Jun;15(2):396-404. doi: 10.1007/s12017-013-8227-0. Epub 2013 Apr 6.
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Inflammation and immune system interactions in atherosclerosis.动脉粥样硬化中的炎症和免疫系统相互作用。
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Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis.FOXP3+ 调节性 T 细胞耗竭可促进高胆固醇血症和动脉粥样硬化。
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Deficiency for costimulatory receptor 4-1BB protects against obesity-induced inflammation and metabolic disorders.缺乏共刺激受体 4-1BB 可预防肥胖引起的炎症和代谢紊乱。
Diabetes. 2011 Dec;60(12):3159-68. doi: 10.2337/db10-1805. Epub 2011 Oct 13.
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