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核受体基因多态性与冠状动脉支架置入术后再狭窄及临床事件风险

Nuclear receptors gene polymorphisms and risk of restenosis and clinical events following coronary stenting.

作者信息

Neugebauer P, Goldbergová-Pávková M, Kala P, Bocek O, Jerábek P, Poloczek M, Vytiska M, Parenica J, Mikulík R, Jarkovský J, Semrád B, Spinar J, Vasků A

机构信息

Interní kardiologická klinika Lékarské fakulty MU a FN Brno.

出版信息

Vnitr Lek. 2009 Dec;55(12):1135-40.

Abstract

INTRODUCTION

Hereditary factors connected with inflammation and fibroproliferation may play important role in restenotic process after coronary stenting. Peroxisome proliferator-activated receptors (PPAR) and retinoic X receptors (RXR) regulate the transcription of crucial genes involved in the glucose and lipid metabolism, inflammation and cell differentiation.

METHODS

In our angiographic and clinical study we assessed the association of gene polymorphisms of L162V for PPAR-alpha, C161T for PPAR-gamma and A(39526)AA for RXR-alpha with the risk of restenosis and cardiac events after coronary stenting. Primary endpoint was diameter stenosis > or = 50% at follow-up angiography. Secondary endpoints were death, myocardial infarction and/or target lesion revascularisation at 12 months, and clinical restenosis. The results were adjusted for known predictors of restenosis. The genotypes were analysed by polymerase chains reaction (PCR) and restriction fragment length polymorphism (RFLP) methods.

RESULTS

Control angiography was performed in 477 of 565 patients (84.4%) with following restenosis rates in genotype subgroups: CC 29.0% vs GC/GG 22.6% (p = 0.33) in L162V, CC 29.9% vs TC/TT 24.6% (p = 0.24) in C161T and A/A 26.9% vs A/AA + AA/AA 35.0% (p = 0.14) in A(39526)AA polymorphisms. The T allele ofC161T polymorphism was associated with lower frequency of clinical restenosis (p = 0.015).

CONCLUSION

We could not find an association of L162V PPAR-alpha, C161T PPAR-gamma and A(39526)AA RXR-alpha gene polymorphisms with angiographic in-stent restenosis or major cardiac events. However, we found the relationship between C161T PPAR-gamma polymorphism and clinical restenosis deserving further study.

摘要

引言

与炎症和纤维增殖相关的遗传因素可能在冠状动脉支架置入术后的再狭窄过程中起重要作用。过氧化物酶体增殖物激活受体(PPAR)和视黄酸X受体(RXR)调节参与葡萄糖和脂质代谢、炎症及细胞分化的关键基因的转录。

方法

在我们的血管造影和临床研究中,我们评估了PPAR-α的L162V、PPAR-γ的C161T以及RXR-α的A(39526)AA基因多态性与冠状动脉支架置入术后再狭窄风险和心脏事件的相关性。主要终点是随访血管造影时直径狭窄≥50%。次要终点是12个月时的死亡、心肌梗死和/或靶病变血管重建,以及临床再狭窄。结果针对已知的再狭窄预测因素进行了校正。通过聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)方法分析基因型。

结果

565例患者中的477例(84.4%)进行了对照血管造影,各基因型亚组的再狭窄率如下:L162V中,CC为29.0%,GC/GG为22.6%(p = 0.33);C161T中,CC为29.9%,TC/TT为24.6%(p = 0.24);A(39526)AA多态性中,A/A为26.9%,A/AA + AA/AA为35.0%(p = 0.14)。C161T多态性的T等位基因与临床再狭窄的较低发生率相关(p = 0.015)。

结论

我们未发现PPAR-α的L162V、PPAR-γ的C161T和RXR-α的A(39526)AA基因多态性与血管造影显示的支架内再狭窄或主要心脏事件之间存在关联。然而,我们发现C161T PPAR-γ多态性与临床再狭窄之间的关系值得进一步研究。

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