Schillinger Martin, Exner Markus, Minar Erich, Mlekusch Wolfgang, Müllner Marcus, Mannhalter Christine, Bach Fritz H, Wagner Oswald
Angiology, Department of Laboratory Medicine, University of Vienna, Medical Faculty, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
J Am Coll Cardiol. 2004 Mar 17;43(6):950-7. doi: 10.1016/j.jacc.2003.09.058.
We investigated the association of the heme oxygenase-1 (HO-1) promoter genotype with the inflammatory response and restenosis after balloon angioplasty.
Heme oxygenase-1, which is induced by balloon angioplasty, can inhibit neointima formation and vascular remodeling. A dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates HO-1 gene transcription. Short (<25 guanosine thymidine [GT]) repeats are associated with a 10-fold greater up-regulation of HO-1 than are longer repeats.
We studied 381 consecutive patients who underwent femoropopliteal balloon angioplasty (n = 210) and comparison groups with femoropopliteal stenting (n = 68) and lower limb angiography (n = 103). C-reactive protein (CRP) was measured at baseline, 24, and 48 h. We evaluated patency at six months by duplex sonography and assessed the association of the length of GT repeats in the HO-1 gene promoter with postintervention CRP and restenosis.
Restenosis within six months was found in 74 patients (35%) after balloon angioplasty and in 21 patients (31%) after stenting. After balloon angioplasty, carriers of the short length (<25 GT) dinucleotide repeats had a lower postintervention CRP at 24 h (p = 0.009) and 48 h (p < 0.001) and a reduced risk for restenosis (adjusted relative risk 0.43, 95% confidence interval: 0.24 to 0.71, p < 0.001) compared with patients with longer alleles. After stenting or angiography, we found no association between the HO-1 genotype with CRP or restenosis.
The HO-1 promoter genotype that controls the degree of HO-1 up-regulation in response to stress stimuli is associated with the postintervention inflammatory response and the restenosis risk after balloon angioplasty.
我们研究了血红素加氧酶-1（HO-1）启动子基因型与球囊血管成形术后炎症反应及再狭窄之间的关联。
球囊血管成形术可诱导血红素加氧酶-1生成，该酶能抑制内膜增生和血管重塑。HO-1基因启动子中的二核苷酸重复序列呈现长度多态性，可调节HO-1基因转录。短（<25个鸟苷胸腺嘧啶[GT]）重复序列与HO-1上调的关联程度比长重复序列高10倍。
我们研究了381例连续接受股腘动脉球囊血管成形术的患者（n = 210）以及股腘动脉支架置入术（n = 68）和下肢血管造影术（n = 103）的对照组。在基线、24小时和48小时测量C反应蛋白（CRP）。我们通过双功超声评估6个月时的血管通畅情况，并评估HO-1基因启动子中GT重复序列长度与干预后CRP及再狭窄之间的关联。
球囊血管成形术后74例患者（35%）和支架置入术后21例患者（31%）出现6个月内再狭窄。球囊血管成形术后，短长度（<25 GT）二核苷酸重复序列携带者在24小时（p = 0.009）和48小时（p < 0.001）时干预后CRP较低，与长等位基因患者相比，再狭窄风险降低（调整后相对风险0.43，95%置信区间：0.24至0.71，p < 0.001）。在支架置入术或血管造影术后，我们未发现HO-1基因型与CRP或再狭窄之间存在关联。
控制HO-1在应激刺激下上调程度的HO-1启动子基因型与球囊血管成形术后干预后炎症反应及再狭窄风险相关。
