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愤怒基因启动子的-374T/A变异与冠状动脉支架置入术后的临床再狭窄相关。

The -374T/A variant of the rage gene promoter is associated with clinical restenosis after coronary stent placement.

作者信息

Falcone C, Emanuele E, Buzzi M P, Ballerini L, Repetto A, Canosi U, Mazzucchelli I, Schirinzi S, Sbarsi I, Boiocchi C, Cuccia M

机构信息

Department of Cardiology, University Hospital Foundation IRCCS San Matteo, Pavia, Italy.

出版信息

Int J Immunopathol Pharmacol. 2007 Oct-Dec;20(4):771-7. doi: 10.1177/039463200702000413.

Abstract

Upregulation of the receptor for advanced glycation end products (RAGE) may play a crucial role in neointimal formation upon vessel injury. The -374T/A variant of the RAGE gene promoter, which has been associated with an altered expression of the cell-surface receptor, could exert a protective effect toward the development of vascular disease. The aim of this study is to determine the impact of this common genetic variant in the occurrence of clinical in-stent restenosis after coronary stent implantation. The -374T/A polymorphism of the RAGE gene promoter was evaluated by PCR-RFLPs in 267 patients with coronary artery disease who underwent coronary stent implantation and a subsequent coronary angiography 6-9 months later for suspected restenosis. In-stent restenosis was assessed by means of quantitative angiography. Carriers of the -374AA genotype showed a significantly reduced risk of developing restenosis after percutaneous transluminal intervention than non-carriers. To determine whether the protective effect of the homozygous AA genotype toward clinical restenosis was independent of potential confounders, we performed multivariable logistic regression analysis. After allowance for clinical and biochemical risk factors and stent length, the AA genotype remained significantly associated with a reduced prevalence of in-stent restenosis. No relation was evident between the RAGE genotype and established cardiovascular risk factors. In conclusion, the -374AA genotype of the RAGE gene promoter could be associated with a reduced risk of in-stent restenosis after coronary stent implantation.

摘要

晚期糖基化终末产物受体(RAGE)的上调可能在血管损伤后的新生内膜形成中起关键作用。RAGE基因启动子的-374T/A变异与细胞表面受体表达的改变有关,可能对血管疾病的发展具有保护作用。本研究的目的是确定这种常见基因变异对冠状动脉支架植入术后临床支架内再狭窄发生的影响。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLPs)对267例冠状动脉疾病患者的RAGE基因启动子-374T/A多态性进行评估,这些患者接受了冠状动脉支架植入术,并在6-9个月后因疑似再狭窄接受了冠状动脉造影。通过定量血管造影评估支架内再狭窄情况。-374AA基因型携带者经皮腔内介入治疗后发生再狭窄的风险明显低于非携带者。为了确定纯合子AA基因型对临床再狭窄的保护作用是否独立于潜在混杂因素,我们进行了多变量逻辑回归分析。在考虑临床和生化危险因素及支架长度后,AA基因型仍与支架内再狭窄患病率降低显著相关。RAGE基因型与已确定的心血管危险因素之间无明显关系。总之,RAGE基因启动子的-374AA基因型可能与冠状动脉支架植入术后支架内再狭窄风险降低有关。

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