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A1166C polymorphism of the angiotensin II type 1 receptor gene and risk of adverse events after coronary catheter interventions

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AMERICAN HEART JOURNAL 2000年第1期140卷 170-175页

作者： Stangl, K Cascorbi, I Stangl, V Laule, M Mrozikiewicz, PM Schwarz, M Felix, SB Theres, H Baumann, G Roots, I Humboldt Univ Univ Klin Charite Med Klin & Poliklin Schwerpunkt Kardiol Angiol & Pneumol D-10117 Berlin Germany Humboldt Univ Univ Klin Charite Inst Klin Pharmakol D-10117 Berlin Germany

Background Contradictory reports exist concerning the role of the angiotensin II type 1 receptor A1166C polymorphism as a coronary risk factor. Moreover, it is unknown whether the A1166C polymorphism is associated with thrombotic complications after coronary catheter interventions. Methods We investigated the role of the A1166C polymorphism as a risk factor in 1000 patients with coronary artery disease (CAD) and in 1000 age- and sex-matched controls. A total of 649 patients receiving interventions (270 coronary angioplasty, 102 atherectomy, and 277 stenting) were investigated for a 30-day composite end point including target vessel revascularization, myocardial infarction, or death. Results The composite end point was reached by 42 patients (6.5%) without evidence that the C allele was associated with excess procedural risk (odds ratio 0.93;95% confidence interval 0.79-1.75;P = .82). Further analyses by device failed to show linkage with adverse events complicating coronary angioplasty, atherectomy, and stenting. Moreover, in the entire CAD group (n = 1000), the polymorphism even showed a trend to underrepresentation (odds ratio 0.83;95% confidence interval 0.69-1.004 P = .054). Conclusions These results indicate that the A1166C polymorphism neither represents a risk Factor for adverse events complicating coronary interventions nor seems to have significant impact on further long-term processes such as development and severity of CAD.

关键词：血管成形术经腔经皮冠状动脉/方法病例对照研究置信区间冠心病/诊断冠心病/遗传学冠心病/治疗冠状动脉血栓形成/流行病学冠状动脉血栓形成/病因学冠状动脉血栓形成/遗传学冠状动脉血栓形成/治疗发病率比值比多态现象遗传概率预后受体血管紧张素 1型受体血管紧张素 2型受体血管紧张素/遗传学参考值危险因素老年人女(雌)性人类男(雄)性中年人

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Angiotensinogen M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease

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AMERICAN HEART JOURNAL 1999年第4期137卷 698-705页

作者： Winkelmann, BR Russ, AP Nauck, M Klein, B Böhm, BO Maier, V Zotz, R Matheis, G Wolf, A Wieland, H Gross, W Galton, DJ März, W Ludwigshafen Heart Ctr Dept Cardiol Ludwigshafen Germany Univ Frankfurt Dept Med D-6000 Frankfurt Germany Univ Frankfurt Dept Heart Surg D-6000 Frankfurt Germany Univ Frankfurt Dept Biochem D-6000 Frankfurt Germany Univ Freiburg Dept Med Div Clin Chem D-7800 Freiburg Germany Univ Ulm Dept Med Ulm Germany Univ Dusseldorf Inst Blood Transfus & Hemostasiol D-4000 Dusseldorf Germany St Bartholomews Hosp Dept Metab & Genet London England

Background Genes encoding components of the renin-angiotensin system have been associated with elevated blood pressure (BP) and an increased risk of coronary artery disease. To explore the role of the angiotensinogen (AGT) gene in coronary atherosclerosis and thrombosis, we studied the effect of the AGT M235T gene variant on plasma AGT levels and BP in patients with coronary artery disease and in the subgroup of survivors of myocardial infarction as compared with angiographically defined control subjects. Methods and Results This was a case-control study of 301 white male subjects examined at Frankfurt University medical center. Plasma AGT levels increased stepwise according to the number of T235 alleles present (no T235 allele, 14.8 +/- 3.9 nmol/L;1 allele, 15.7 +/- 5.1 nmol/L;2 alleles, 17.3 +/- 4.7 nmol/L;P = .006). In a multivariate model, circulating AGT emerged as the most important predictor of diastolic pressure (P = .001). In addition, AGT M235T gene polymorphism remained a significant predictor of diastolic BP in a multivariate model adjusted for age, body mass index, fasting glucose, apolipoprotein B, presence of coronary artery disease, and treatment with antihypertensive agents (P < .05). Finally, homozygosity for T235 was associated with increased univariate risk of coronary artery disease and myocardial infarction (odds ratio estimates 1.5;95% confidence intervals 1.1 to 2.1, P = .03, and 1.0 to 2,1, P = .05, respectively). Conclusions The significant relations observed between the AGT M235T variant, its protein product, and the cardiovascular disease phenotypes provide evidence for a possible role of elevated circulating AGT in the pathogenesis of coronary artery disease.

关键词：等位基因血管紧张素原/血液血管紧张素原/遗传学血压/遗传学心血管疾病/遗传学病例对照研究冠状动脉血栓形成/遗传学基因频率基因型多元分析心肌梗死/遗传学比值比肽基二肽酶A/血液多态现象遗传肾素-血管紧张素系统/遗传学危险因素人类男(雄)性中年人

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Pl^A polymorphism of glycoprotein IIIa and risk of adverse events after coronary stent placement

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第1期36卷 84-89页

作者： Kastrati, A Koch, W Gawaz, M Mehilli, J Böttiger, C Schömig, K von Beckerath, N Schömig, A Deutsch Herzzentrum Munich D-80636 Munich Germany Tech Univ Munich Med Klin Rechts Isar 1 D-8000 Munich Germany

OBJECTIVE We designed this prospective study to test the hypothesis that platelet antigen (P1(A)) polymorphism of glycoprotein (GP) IIIa is associated with an increased risk for adverse events after coronary stent placement. BACKGROUND Platelets play a central role in arterial thrombosis. The P1(A) polymorphism of GP IIIa, a constituent of the fibrinogen receptor, may influence the platelet function and, thereby, the early outcome of patients after coronary stent placement. METHODS The study included 1,759 consecutive patients with stable or unstable angina and successful coronary stent placement. Platelet antigen genotypes were determined by allele-specific restriction enzyme analysis. The end point of the study was a composite of death, myocardial infarction and urgent revascularization during the first 30 days after stent placement. RESULTS The P1(A) genotype of the patients included was: 70.2% were homozygous for platelet antigen 1 (P1(A1)), 2.6% homozygous for platelet antigen 2 (P1(A2)), and 27.2% were heterozygous (p1(A1/A2)). The incidence of the composite end point was 5.5% among P1(A2) carriers and 5.4% in homozygous P1(A1) subjects (p = 0.94). It was 5.4% in p1(A1/A1) patients, 4.8% in p1(A1/A2) patients and 13.0% in P1(A2/A2) patients (P = 0.06). The combined incidence of death or myocardial infarction was 4.3% in P1(A1/A2) p1(A2/A2) patients (p = 0.02). CONCLUSION The isolated presence of the p1(A2) allele in heterozygous patients is not associated with anp detectable increase in the risk for an adverse 30-day outcome after coronary stenting. This study suggests also that an increased risk is likely to be present in homozygous carriers of the P1(A2) allele, but this should be confirmed in a much larger series of patients. (J Am Coil Cardiol 2000;36: 84-9) (C) 2000 by the American College of Cardiology.

关键词：等位基因心绞痛/外科学抗原 CD/遗传学抗原 CD/代谢抗原人血小板/血液抗原人血小板/遗传学冠状血管造影术冠状动脉血栓形成/血液冠状动脉血栓形成/并发症冠状动脉血栓形成/诊断显像冠状动脉血栓形成/遗传学 DNA/分析 DNA引物/化学表位/血液表位/遗传学遗传标记基因型整合素β3 整合素类/血液整合素类/遗传学心肌梗死/血液心肌梗死/诊断显像心肌梗死/病因学比值比血小板膜糖蛋白类/遗传学血小板膜糖蛋白类/代谢聚合酶链反应多态现象遗传预后前瞻性研究危险因素支架/副作用老年人女(雌)性人类男(雄)性中年人

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Polymorphism of platelet glycoprotein IIb and risk of thrombosis and restenosis after coronary stent placement

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第9期84卷 987-991页

作者： Böttiger, C Kastrati, A Koch, W Mehilli, J von Beckerath, N Dirschinger, J Gawaz, M Schömig, A Deutsch Herzzentrum Munich D-80636 Munich Germany Tech Univ Munich Med Klin Rechts der Isar 1 D-8000 Munich Germany

Both glycoprotein (GP) IIb and IIIa of platelet fibrinogen receptor are polymorphic proteins. Unlike GPIIIa, there is little information about the clinical significance of the GPIIb polymorphism. We designed this prospective study to assess whether patients with the human platelet antigen (HPA)-3 polymorphism of GPIIb are more susceptible to developing thrombosis and restenosis after coronary stent placement. We included 2,178 consecutive patients with coronary artery disease who underwent intracoronary stent implantation, 789 (36.2%) with HPA-3a/a, 1,023 (47.0%) with HPA-3a/b, and 366 (16.8%) with HPA-3b/b genotype. The incidence of stent thrombosis was 1.7% in HPA-3a/a, 1.7% in HPA-3a/b, and 1.6% in HPA-3b/b patients (p = 0.999). The incidence of stent restenosis wets 37.3% in HPA-3a/a, 36.2% in HPA-3a/b, and 34.6% in HPA-3b/b patients (p = 0.724). Event-free survival 1 year after stent placement was 76.1% for HPA-3a/a, 76.5% for HPA-3a/b, and 76.4% for HPA-3b/b patients (p = 0.968). We conclude that the HPA-3 polymorphism of platelet GPIIb is not associated with an increase in the risk of thrombosis and restenosis over 1 year after coronary stent placement. These data indicate that unlike the HPA-1 polymorphism of GPIIIa, the HPA-3 polymorphism of GPIIb may mot serve as a useful genetic marker for the risk assessment of patients treated with intracoronary stenting. (C) 1999 by Excerpta Medica, Inc.

关键词：血管成形术经腔经皮冠状动脉/仪器和设备冠状血管造影术冠心病/遗传学冠心病/治疗冠状动脉血栓形成/遗传学冠状动脉血栓形成/治疗随访研究基因频率疾病遗传易感性/遗传学基因型血小板糖蛋白GPⅡb-Ⅲa复合物/遗传学多态现象遗传/遗传学前瞻性研究复发支架治疗结果成年人老年人女(雌)性人类男(雄)性中年人

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