编码生长因子转化生长因子-β1（TGF-β1）、血小板衍生生长因子B（PDGFB）、表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子-A（VEGF-A）的基因多态性与接受裸金属支架治疗的稳定型冠状动脉疾病患者再狭窄过程之间的关系。
The Relationships between Polymorphisms in Genes Encoding the Growth Factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A and the Restenosis Process in Patients with Stable Coronary Artery Disease Treated with Bare Metal Stent.
作者信息
Osadnik Tadeusz, Strzelczyk Joanna Katarzyna, Reguła Rafał, Bujak Kamil, Fronczek Martyna, Gonera Małgorzata, Gawlita Marcin, Wasilewski Jarosław, Lekston Andrzej, Kurek Anna, Gierlotka Marek, Trzeciak Przemysław, Hawranek Michał, Ostrowska Zofia, Wiczkowski Andrzej, Poloński Lech, Gąsior Mariusz
机构信息
Third Department of Cardiology, School of Medicine with the Division of Dentistry, Medical University of Silesia, Zabrze, Poland.
Genomics Laboratory, Kardio-Med Silesia Science and Technology Park, Zabrze, Poland.
出版信息
PLoS One. 2016 Mar 1;11(3):e0150500. doi: 10.1371/journal.pone.0150500. eCollection 2016.
BACKGROUND
Neointima forming after stent implantation consists of vascular smooth muscle cells (VSMCs) in 90%. Growth factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A play an important role in VSMC proliferation and migration to the tunica intima after arterial wall injury. The aim of this paper was an analysis of functional polymorphisms in genes encoding TGF-β1, PDGFB, EGF, bFGF and VEGF-A in relation to in-stent restenosis (ISR).
MATERIALS AND METHODS
265 patients with a stable coronary artery disease (SCAD) hospitalized in our center in the years 2007-2011 were included in the study. All patients underwent stent implantation at admission to the hospital and had another coronary angiography performed due to recurrence of the ailments or a positive result of the test assessing the coronary flow reserve. Angiographically significant ISR was defined as stenosis >50% in the stented coronary artery segment. The patients were divided into two groups-with angiographically significant ISR (n = 53) and without significant ISR (n = 212). Additionally, the assessment of late lumen loss (LLL) in vessel was performed. EGF rs4444903 polymorphism was genotyped using the PCR-RFLP method whilst rs1800470 (TGFB1), rs2285094 (PDGFB) rs308395 (bFGF) and rs699947 (VEGF-A) were determined using the TaqMan method.
RESULTS
Angiographically significant ISR was significantly less frequently observed in the group of patients with the A/A genotype of rs1800470 polymorphism (TGFB1) versus patients with A/G and G/G genotypes. In the multivariable analysis, LLL was significantly lower in patients with the A/A genotype of rs1800470 (TGFB1) versus those with the A/G and G/G genotypes and higher in patients with the A/A genotype of the VEGF-A polymorphism versus the A/C and C/C genotypes. The C/C genotype of rs2285094 (PDGFB) was associated with greater LLL compared to C/T heterozygotes and T/T homozygotes.
CONCLUSIONS
The polymorphisms rs1800470, rs2285094 and rs6999447 of the TGFB1, PDGFB and VEGF-A genes, respectively, are associated with LLL in patients with SCAD treated by PCI with a metal stent implantation.
背景
支架植入后形成的新生内膜90%由血管平滑肌细胞（VSMC）组成。生长因子转化生长因子-β1（TGF-β1）、血小板衍生生长因子-B（PDGFB）、表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子-A（VEGF-A）在动脉壁损伤后VSMC增殖及向内膜迁移过程中起重要作用。本文旨在分析编码TGF-β1、PDGFB、EGF、bFGF和VEGF-A的基因功能多态性与支架内再狭窄（ISR）的关系。
材料与方法
纳入2007年至2011年在本中心住院的265例稳定型冠状动脉疾病（SCAD）患者。所有患者入院时均接受了支架植入术，并因病情复发或评估冠状动脉血流储备的检查结果呈阳性而再次进行冠状动脉造影。血管造影显示的显著ISR定义为支架置入的冠状动脉节段狭窄>50%。患者分为两组——血管造影显示有显著ISR的患者（n = 53）和无显著ISR的患者（n = 212）。此外，还对血管的晚期管腔丢失（LLL）进行了评估。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对EGF rs4444903多态性进行基因分型，而采用TaqMan方法测定rs1800470（TGFB1）、rs2285094（PDGFB）、rs308395（bFGF）和rs699947（VEGF-A）。
结果
rs1800470多态性（TGFB1）A/A基因型患者组中血管造影显示的显著ISR发生率明显低于A/G和G/G基因型患者。在多变量分析中，rs1800470（TGFB1）A/A基因型患者的LLL明显低于A/G和G/G基因型患者，而VEGF-A多态性A/A基因型患者的LLL高于A/C和C/C基因型患者。与C/T杂合子和T/T纯合子相比，rs2285094（PDGFB）的C/C基因型与更大的LLL相关。
结论
TGFB1、PDGFB和VEGF-A基因的多态性rs1800470、rs2285094和rs6999447分别与接受金属支架植入PCI治疗的SCAD患者的LLL相关。
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