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| 1 | The microsatellite polymorphism of heme oxygenase-1 is associated with baseline plasma IL-6 level but not with restenosis after coronary in-stenting显示文摘Background Vascular smooth muscle cells (VSMCs) can express heme-oxygenase (HO), a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide (CO). VSMC-derived CO can suppress VSMC proliferation and may serve as an antiproliferation factor. The promoter region of HO-1 shows a polymorphism with different (GT)_n repeats that has been reported to differently induce gene expression. The objective of this study was to examine the effect of this variation on the occurrence of restenosis after in-stent treatment in patients with coronary artery disease. Methods Candidates who underwent coronary stent implantation were genotyped for the HO-1 promoter polymorphism using polymerase chain reaction (PCR) and automated DNA capillary sequencer. Serum levels of IL-6 and C-reactive protein (CRP) were obtained at baseline, 24 hours and 48 hours after stenting. The primary end point for the study was angiographic evidence of in-stent restenosis at 6 months. All parameters for evaluation of restenosis were analysed by quantitatve computer-assisted angiographic analysis (QCA). Results One hundred and eighty-seven patients who underwent coronary stent implantation were studied of whom 27.8% showed ≥50% restenosis after 6 months. The distribution of (GT)_n repeats of all patients in the promoter region of HO-1 genotype ranged from 22 to 42, with (GT)_ 25 and (GT)_ 32 being the two most common alleles. The allelic repeats were divided into the short class (S) with 29 (GT)_n, the middle class (M) with 30-37 (GT)_n and the long class (L) with 38 (GT)_n. There was no significant difference in the restenosis between the genotype groups or between post operation levels of inflammation markers, but carriers of the S allele (n=120) had 33.3% lower baseline IL-6 compared with non-S carriers (n=67, P=0.0008). Conclusions Although no association was observed between the HO-1 promoter polymorphism aod coronary in-stent restenosis following the stent procedure, the association with plasma IL-6 levels suggests that HO-1 S allele might protect from the atherosclerotic inflammatory process. | LI Ping Mohamed A. Elrayess Abuzeid H. Gomma Jutta Palmen Emma Hawe Kim M. Fox Steve E. Humphries | 2005 | Chinese Medical Journal2005，，18： | 6 |
| 2 | Inflammatory response to coronary artery bypass surgery: Does the heme-oxygenase-1 gene microsatellite polymorphism play a role?显示文摘Background Heme-oxygenase 1 (HO-1) is a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide (CO) and may have significant anti-inflammatory function. The HO-1 gene promoter region shows microsatellite polymorphism with different (GT)n repeats, reported to differently induce gene expression, with the short allele associated with higher gene expression. We measured the acute inflammatory response using coronary artery bypass surgery (CABG) as a well-characterized and uniform stimulus and examined the correlation between levels of IL-6, C-reactive protein (CRP) and fibrinogen and their relationship to HO-1 genotype.Methods Two hundred and seventy-five consecutive patients undergoing CABG were genotyped for the HO-1 promoter polymorphism using PCR and automated DNA capillary sequencer. IL-6, CRP and fibrinogen were measured at baseline and 6, 24, 48, 72, 96 and 120 hours after CABG.Results Complete IL-6,CRP and fibrinogen measures were available in 220 patients. Before surgery IL-6 levels showed a strong correlation with CRP and fibrinogen ( r =0.48, P <0.0001; r =0.41, P <0.0001 respectively), with a significant correlation between CRP and fibrinogen ( r =0.61, P <0.0001). All three acute phase reactants showed a significant increase after CABG. After surgery, peak IL-6 was strongly correlated with peak CRP ( r =0.34, P =0.0009) but not with peak fibrinogen ( r =0.15, P =0.13), while peak CRP and peak fibrinogen were significantly correlated ( r =0.415, P <0.0001). HO-1 allelic repeats ranged from 22-42, with (GT) 25 and (GT) 32 being the two most common alleles, and subsequently divided into three groups according to previous published work: <30(GT)n were designated as S (short), 30-37(GT)n as M (middle) and long repeats with >37(GT)n as L (long); allele frequency 0.35, 0.58 and 0.07 respectively. Baseline CRP differed by genotype: those carrying at least one long allele having higher CRP than those with no long allele (3.76±0.79 vs. 2.07±0.17, P =0.013). Conversely, those carrying at least one short allele had higher fibrinogen levels than those with no short allele (3.83±0.79 vs. 3.51±0.88, P =0.006). Conclusions There is a strong correlation between the measured acute phase reactants both at baseline and after the inflammatory response to CABG in patients with coronary disease. There was an association between the HO-1 microsatellite polymorphism and CRP and fibrinogen levels at baseline but there was no similar association following CABG. This may indicate that HO-1 is associated with chronic atherosclerotic inflammatory processes rather than acute. | LI Ping Jules Sanders Emma Hawe David Brull Hugh Montgomery Steve Humphries | 2005 | Chinese Medical Journal2005，，15： | 2 |
| 3 | 冠脉旁路搭桥术后的炎症反应:HO-1基因多态的影响显示文摘目的 观察冠状动脉旁路 (CABG)手术为刺激手段 ,研究术后炎性标记物白介素 6 (IL 6 ) ,C反应蛋白 (CRP)及纤维蛋白原 (fibrinogen ,Fb)的水平及其相关性 ,并探讨基因变量对它们的影响。方法 2 2 0名符合入选条件的行CABG术的患者 ,用PCR和DNA测序仪分析其HO 1基因启动子部位GT重复序列的长短 ;于手术前及术后 6 ,2 4 ,4 8,72 ,96和 12 0h分别测IL 6 ,CRP和Fb值。结果 术前CRP及Fb值与IL 6水平明显相关 (分别为r =0 .4 8,P <0 .0 0 0 1;r =0 .4 1,P <0 .0 0 0 1) ,术前三者均显著升高 ,CRP峰浓度与IL 6峰浓度有很强的相关性 (r =0 .34,P =0 .0 0 0 9) ,但后者的Fb峰值无关 (r=0 .15 ,P =0 .13)。基础CRP值在HO 1各基因组间存在明显差异 ,携带较长GT重复序列者较之非长GT重复序列携带者 ,CRP值较高 (3.76± 0 .79和 2 .0 7± 0 .17,P =0 .0 13) ;术后则各基因型组间水平相似。结论 炎症标志物的水平间存在相关性 ,HO 1基因多态只与术前基础的CRP和Fb值有关 ,提示它可能只影响疾病过程的慢性炎症状态 ,从而可能影响炎性疾病的发生 ,而非急性炎症反应。 | 李萍 Jules Sanders Emma Hawe Jutta Palmen David Brull Sukhbir Dhamrait Jayshree Acharya Hugh Montgomery Steve Humphries | 2003 | 介入放射学杂志2003，12，S1： | 0 |
| 4 | HO基因启动子GT序列变量与冠脉支架术后再狭窄显示文摘目的 血管平滑肌细胞可表达血红素氧化酶 (HO) ,后者是降解血红素成为胆红素、亚铁及一氧化碳的限速酶。血管平滑肌来源的一氧化碳已证实能抑制血管平滑肌增殖。研究表明Ⅰ型HO基因启动子部位的GT重复序列长短变量可影响该基因的转录水平 ,较短GT重复序列能使该基因转录活性增加 ,因而对多个疾病的发生具有保护作用。本研究的目的为观察GT重复序列长短变量差异对冠脉支架置入术后再狭窄的影响。方法 187例成功行冠脉支架置入术的患者 ,6个月随访时间 2 7.8%管腔再狭窄超过 5 0 %。用PCR和DNA测序仪确定HO基因启动子部位的GT重复次数。高敏法测定术前及术后 2 4、4 8小时血浆中的白介素 6和C反应蛋白水平。结果 各基因型组间术后IL 6和CRP水平以及再狭窄情况无差异 ,但携带较短GT序列者 (n =12 0 )术前基础IL 6值比非短GT序列携带者 (n =6 7)低大约 33.3% (P =0 .0 0 0 8)。结论 尽管未能说明HO 1基因多态能影响支架置入术后的炎性水平及再狭窄情况 ,但它和基础IL 6浓度的关系提示 。 | 李萍 Mohamed A.Elrayess Abuzeid H.Gomma Jutta Palmen Emma Hawe Kim M.Fox Steve E.Humphries | 2003 | 介入放射学杂志2003，12，S1： | 0 |
| 5 | 血红素氧化酶1基因多态和冠状动脉旁路移植后的炎症反应显示文摘背景:血红素氧化酶1是降解血红素生成胆红素、亚铁及一氧化碳过程的限速酶,具有重要的抗炎功能,其启动子部位GT重复序列的多态性可使该基因表达的水平不同,重复序列较短者基因转录活性较高。目的:观察冠状动脉旁路移植术后炎性标记物白细胞介素6,C-反应蛋白及纤维蛋白原的水平及其相关性,探讨血红素氧化酶1基因变量对它们的影响。设计、时间及地点:观察性试验,于2003年在英国伦敦大学学院心血管遗传病学中心完成。对象:220例符合入选条件的行冠状动脉旁路移植术的患者,男179例,女41例,年龄(63.34±9.64)岁。方法:PCR方法和DNA测序仪分析其血红素氧化酶1基因启动子部位GT重复序列的长短;于手术前及术后6,24,48,72,96,120h分别测白细胞介素6、C-反应蛋白和纤维蛋白原水平。主要观察指标:血红素氧化酶1基因启动子部位GT重复序列的长短;手术前及术后不同时间白细胞介素6、C-反应蛋白和纤维蛋白原水平。结果:术前白细胞介素6水平与C-反应蛋白及纤维蛋白原值显著相关(r=0.48,P<0.0001;r=0.41,P<0.0001),术后3者均显著升高,白细胞介素6峰质量浓度与C-反应蛋白峰质量浓度显著相关(r=0.34,P=0.0009),但与纤维蛋白原峰值无明显相关性(r=0.15,P=0.13)。术前C-反应蛋白值在血红素氧化酶1各基因组间存在明显差异,长GT重复序列者比短GT重复序列携带者高[(3.76±0.79),(2.07±0.17)mg/L,P=0.013];术后则各基因型组间水平相似。结论:炎症标志物的水平间存在相关性,血红素氧化酶1基因多态只与术前的基础C-反应蛋白和纤维蛋白原值有关,提示其可能只影响疾病的慢性炎症状态,从而影响炎性疾病的发生,而非急性炎症反应。 | 李萍 Jules Sanders Emma Hawe David Brull Jutta Palmen Jayshree Achary Hugh Montgomery Steve E.Humphries | 2009 | 中国组织工程研究与临床康复2009，13，22： | 0 |
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