Department of Cardiology, Academic Medical Center, University of Amsterdam, The Netherlands.
Pharmacogenet Genomics. 2010 Sep;20(9):544-52. doi: 10.1097/FPC.0b013e32833d7b29.
Restenosis after percutaneous coronary intervention (PCI) remains an issue even in the drug-eluting stent era. Genetic polymorphisms may provide insight in the pathogenesis of restenosis and may help in the stratification of patients at risk for restenosis. The aim of this study was to examine whether polymorphisms at the toll-like receptor 4 (TLR4) locus, that are associated with impaired innate immune system and with an increased risk of cardiovascular events, were associated with clinical and/or angiographic restenosis after PCI.
The GENetic Determinants of Restenosis (GENDER) project was a prospective, multicenter study that enrolled 3146 consecutive patients after successful PCI. Frequencies of the TLR4 896A/G (Asp299Gly; rs4986790) and 1196C/T (Thr399Ile; rs4986791) polymorphisms and haplotypes were assessed. Patients were followed up for 1 year and in a subgroup of 406 patients angiographic follow-up was obtained.
We included a total of 2682 patients that underwent successful PCI. There was no association between genotypes and the risk of target vessel revascularization at 1-year or late luminal loss at 6-months angiographic follow-up (P=0.53 and 0.44, respectively). Absence of association with target lesion revascularization and late luminal loss was replicated in the GEnetic risk factors for In-Stent Hyperplasia study Amsterdam (GEISHA) cohort study of 674 patients and in a subgroup of 550 patients with angiographic follow-up available (P=0.26, and 0.86, respectively). Moreover, in both the studies, no significant differences between haplotypes A/C and G/T were observed for target vessel revascularization at late luminal loss.
Although inflammation has been implicated in the pathophysiology of restenosis, the 896A/G and 1196C/T polymorphisms or haplotypes based on these polymorphisms at the TLR4 locus are not associated with an increased risk of target vessel revascularization or angiographic restenosis after PCI. These polymorphisms are not useful for pre-PCI identification of patients at risk for restenosis.
即使在药物洗脱支架时代，经皮冠状动脉介入治疗（PCI）后的再狭窄仍然是一个问题。遗传多态性可能为再狭窄的发病机制提供深入了解，并有助于对再狭窄风险患者进行分层。本研究旨在探讨 Toll 样受体 4（TLR4）基因座的多态性是否与 PCI 后临床和/或血管造影再狭窄有关，这些多态性与先天免疫系统受损和心血管事件风险增加有关。
GENetic Determinants of Restenosis（GENDER）项目是一项前瞻性、多中心研究，共纳入 3146 例成功 PCI 后的连续患者。评估 TLR4 896A/G（Asp299Gly；rs4986790）和 1196C/T（Thr399Ile；rs4986791）多态性和单倍型的频率。患者随访 1 年，其中 406 例患者进行了血管造影随访。
共纳入 2682 例成功 PCI 的患者。基因型与 1 年时靶血管血运重建风险或 6 个月血管造影随访时晚期管腔丢失无相关性（P=0.53 和 0.44）。在 674 例 GEISHA 研究阿姆斯特丹（GEISHA）队列研究和 550 例有血管造影随访的亚组中，靶病变血运重建和晚期管腔丢失与无相关性的结果也得到了复制（P=0.26 和 0.86）。此外，在这两项研究中，TLR4 基因座上基于这些多态性的单倍型 A/C 和 G/T 之间在晚期管腔丢失时的靶血管血运重建没有显著差异。
尽管炎症被认为是再狭窄的病理生理学机制之一，但 TLR4 基因座的 896A/G 和 1196C/T 多态性或基于这些多态性的单倍型与 PCI 后靶血管血运重建或血管造影再狭窄的风险增加无关。这些多态性不能用于 PCI 前识别再狭窄风险患者。
