1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients
1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients
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DOI：
10.1016/j.mad.2005.03.007
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发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Mocchegiani, E
中科院分区：
文献类型：
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作者：
Giacconi, R;Caruso, C;Mocchegiani, E
2 型糖尿病 (NIDDM) 患者面临大血管疾病并发症的风险，例如心肌梗死 (MI) 或斑块破裂引起的中风。细胞因子在斑块脆弱性中发挥着关键作用。 IFN-γ 抑制胶原蛋白合成，从而影响斑块稳定性。高IL-6、TNF-α和血脂异常是血栓形成的危险因素。动脉粥样硬化斑块中 HSP70 的异常增加可能会导致慢性炎症引起的斑块不稳定和破裂，从而上调人单核细胞中促炎细胞因子（IL-6 和 TNF-α）的表达。对位于 HSP70-2 基因第 1267 位编码区的多态性 PstI 位点的研究表明，1313 基因型与 NIDDM 相关。我们对 60 名患有颈动脉狭窄的老年 NIDDM 患者和 107 名老年健康对照者进行了 1267 HSP702 多态性筛查，以确定是否与斑块脆弱存在关联。在患者和健康对照之间观察到不同的基因型分布。相对风险增加与 B 等位基因相关（p = 0.0107；比值比 = 1.861）。根据 B+（AB 和 1313）和 B-（AA）基因型分层，检测斑块内 HSP70-2、IL-6、IFN-γ、TNF-α 基因表达以及甘油三酯、总胆固醇和 LDL 胆固醇的血清水平。还评估了斑块形态（软或纤维钙化）和脑缺血的发生率。与 13- 携带者相比，B+ 患者表现出 HSP70-2、IL-6、IFN-γ、TNF-a 和血脂异常增加。与 B- 患者相比，B+ 患者出现软斑块的频率增加（67% 对比 13%；比值比 13.0，p = 0.0006）。 B+ 基因型中出现脑缺血（发作或短暂性脑缺血发作 (TIA)）的频率高于 13- 基因型（53% 对比 20%；比值比 4.57，p < 0.05）。因此，1267 HSP702 多态性可用于识别有颈动脉斑块破裂和脑缺血风险的 13+ NIDDM 患者。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
Patients with type 2 diabetes mellitus (NIDDM) are at risk for macrovascular disease complications, such as myocardial infarction (MI) or stroke from plaque rupture.Cytokines play a key role in plaque vulnerability. IFN-gamma inhibits collagen synthesis thereby affecting plaque stability. High IL-6, TNF-alpha, and dyslipidemia are risk factors for thrombosis. Abnormal increments of HSP70 in atherosclerotic plaques might lead to plaque instability and rupture caused by chronic inflammation, which up-regulates the expression of pro-inflammatory cytokines (IL-6 and TNF-alpha) in human monocytes. Studies of a polymorphic PstI site lying in the coding region at position 1267 of the HSP70-2 gene have shown that the 1313 genotype is associated with NIDDM. We screened 60 old NIDDM patients with carotid stenosis and 107 old healthy controls for 1267 HSP702 polymorphism in order to establish if an association with plaque frailty exists. Different genotypic distributions were observed between patients and healthy controls. An increased relative risk was associated with the B allele (p = 0.0107; odds ratio = 1.861). HSP70-2, IL-6, IFN-gamma, TNF-alpha gene expressions within the plaques and serum levels of triglyceride, total cholesterol and LDL cholesterol were tested from patients stratified according to their B+ (AB and 1313) and B-(AA) genotypes. Plaque morphology (soft or,fibrous-calcified) and the incidence of cerebral ischaemia were also assessed.B+ patients showed increased HSP70-2, IL-6, IFN-gamma, TNF-a and dyslipidemia as compared to 13- carriers. The frequency of soft plaques increased in B+ in comparison to B-patients (67% versus 13%; odds ratio 13.0, p = 0.0006). A higher frequency of cerebral ischaemia (ictus or transient ischaemic attack (TIA)) was present in B+ than in 13- genotype (53% versus 20%; odds ratio 4.57, p < 0.05) Hence, 1267 HSP702 polymorphism may be of use in identifying 13+ NIDDM patients at risk for carotid plaque rupture and cerebral ischaemia. (c) 2005 Elsevier Ireland Ltd. All rights reserved.