凝血因子Ⅶ与冠心病

冠心病的发生发展与凝血纤溶系统的关系十分密切.凝血因子Ⅶ是凝血过程中的一个重要辅助因子.凝血因子Ⅶ活性(FⅦC)增高被认为与冠心病的发生有关,而遗传因素,即FⅦ基因多态性是影响FⅦC水平的重要因素,所以FⅦ基因多态性与冠心病的关系日益受到关注.本文将对FⅦ的遗传特性、FⅦC及与冠心病的关系作一综述.     

凝血因子Ⅶ与冠心病

冠心痛的发生发展与凝血纤溶系统的关系十分密切。凝血因子Ⅶ是凝血过程中的一个重要辅助因子。凝血因子Ⅶ活性(FⅦc)增高被认为与冠心痛的发生有关，而遗传因素，即FⅦ基因多态性是影响FⅦC水平的重要因素，所以FⅦ基因多态性与冠心痛的关系日益受到关注。本文将对FⅦ的遗传特性、FⅦC及与冠心痛的关系作一综述。     

冠心病患者凝血因子Ⅶ-3230/10 bp基因多态性的检测

目的研究冠心病(CHD)患者凝血因子Ⅶ(FⅦ)-3230/10 bp基因多态性的频率及意义.方法活化FⅦ(RⅦa)测定采用重组可溶性组织因子一期法,FⅦ活性(FⅦc)测定采用凝血一期法,FⅦ总抗原(FⅦag)采用酶联免疫吸附法(ELISA法).多态性分析用PCR-尿素聚丙烯酰胺凝胶电泳法.结果60例FⅦ-3230/10 bp多态性检测发现5例0/10 bp多态性,未检出10/10 bp多态性.10 bp等位基因检出率为8%.在存在0/10 bp基因多态性的病例组的FⅦc,FⅦag比0/0 bp组明显减低.结论FⅦ-323 0/10 bp多态性存在于中国的CHD患者中,它与CHD血浆FⅦc、FⅦag水平有关;患者10 bp等位基因是CHD血栓形成的保护因素.     

冠心病血瘀证凝血因子Ⅶ基因多态性的检测分析

目的探讨凝血因子Ⅶ（FⅦ）基因多态性与冠心病（CHD）心血瘀阻证候度凝血因子Ⅶ活性（FⅦc）的相关性。方法对CHD心血瘀阻证组112例、非心血瘀阻证组108例、非CHD心血瘀阻证组110例和健康对照组100名检测分析FⅦ基因型（M1M1、M1M2、M2M2）和等位基因（M1、M2）及FⅦc。结果CHD心血瘀阻证组在基因型M1M1和等住基因M1频率分布均显著高于健康对照组（P〈0．05）；FⅦ-M1M1基因型的各组受检者FⅦc值的变化呈CHD心血瘀阻证组〉非CHD血瘀证组〉CHD非血瘀证组〉健康对照组递减趋势；而FⅦ-M1M2基因型各组受检者FⅦC值的变化相反，呈现健康对照组〈CHD非血瘀证组〈非CHD心血瘀阻证组〈CHD心血瘀证组的趋势；在三个病变组内，FⅦ基因M1M1型的FⅦC检测值均较M1M2型显著增高。结论FⅦ基因M1M1多态性和M1等住基因与CHD心血瘀阻证相关：FⅦ基因多态性与血浆ⅦC密切相关。     

老年人冠心病与凝血因子Ⅶ基因多态性的关系

近年来．有学者认为外源性凝血途径在血栓形成过程中具有重要意义，凝血因子Ⅶ在外源性凝血途径的启动中起关键性作用，在动脉血栓形成过程中意义重大。凝血因子Ⅶ水平受遗传因素与环境因素及其相互作用的影响，遗传因素主要指存在于凝血因子Ⅶ基因中的多态性．其中比较重要的多态性位点有：（1)位于凝血因子Ⅶ启     

凝血因子Ⅶ与冠心病

冠状动脉粥样硬化斑块破裂诱发血栓形成是急性心肌梗死 (AMI)、不稳定型心绞痛 (UA)及缺血性心脏性猝死的主要病理基础 ;血栓形成又促进了粥样斑块病变的发展 [1] 。凝血因子 VII(FVII)是生理及病理凝血反应的主要始动因子 ,关于 FVII与冠心病(CHD)关系的研究为人们探索 CHD的危险因素及防治措施提供了新的思路。本文综述近年来这方面的研究进展。1　 FVII的结构与功能FVII是由肝细胞分泌的维生素 K依赖性的单链糖蛋白 ,是组织因子 (TF)介导的凝血激活途径的启动酶 ,含 4 0 6个氨基酸 ,分子量 6 0 k D(≈ 6 .0× 10 4 u) ,基…     

宁夏回族人群凝血因子Ⅶ基因HVR4多态性研究

目的探讨宁夏回族人群中凝血因子Ⅶ基因HVR4多态性的分布及其与冠心病和(或)心肌梗死的关系。方法采用病例-对照的方法,通过聚合酶链反应技术,检测105例回族冠心病患者和127名正常回族对照者的凝血因子ⅦHVR4基因型,同时采用重组可溶性组织因子法测定血浆FⅦa水平。结果基因型频率符合Hardy-Wein-berg平衡定律(P>0.05);血浆FⅦa水平在凝血因子Ⅶ基因HVR4各基因型间无显著性差别(P>0.05);HVR4基因多态性在冠心病组与对照组、心肌梗死组与非心肌梗死组间比较差别无显著性(P>0.05)。结论宁夏回族人群中存在凝血因子Ⅶ基因的HVR4多态性,但在冠心病或心肌梗死发病中的作用尚不确定。     

凝血因子Ⅱ、V基因多态性与冠心病的研究

20世纪 90年代中后期 ,凝血因子ⅡＧ2 0 2 1 0Ａ基因突变导致凝血酶原水平增高和凝血因子ⅤＬｅｉｄｅｎ基因突变 ,引起的活化蛋白Ｃ抵抗 (ＡＰＣ Ｒ)作为白种人静脉血栓形成的遗传危险因素在西方国家的流行病学研究中基本得到肯定 ,而与冠心病之间的联系尚有争论。目前国内缺乏此方面的研究报告。本组探讨凝血因子ⅡＧ2 0 2 1 0Ａ和凝血因子ⅤＬｅｉｄｅｎ突变在汉族人冠心病患者和正常人中的发生率 ,并探讨其与冠心病的关系。1 材料与方法 :选择曾于我院住院冠心病患者 2 34例(男 1 82例 ,女 52例 ) ,平均年龄 (61 8± 9 4)岁 ,均符合 1…     

凝血因子Ⅶ水平及其基因多态性与PTE的相关研究

目的探讨FⅦ基因R353Q多态性及血浆FⅦa水平与PTE的相关性。方法收集肺血栓栓塞症(PTE)患者198例和对照组212例;采用PCR-PFLP检测FⅦ基因R353Q多态性,ELISA法测定血浆FⅦa水平。结果①FⅦ基因R353Q单核苷酸多态性(SNP)基因分布频率和等位基因携带频率在病例与对照组差异均无统计学意义(P0.05)。②血浆FⅦa水平PTE组与对照组比较,差异有显著性意义(P=0.000)。③通过非条件Logistic回归模型校正后,吸烟、纤维蛋白原和血浆FⅦa水平是PTE患者的独立危险因素。结论高血浆FⅦa水平是PTE患者的独立危险因素;FⅦ基因R353Q多态性可能不是PTE患者的独立危险因素。     

凝血因子Ⅶ及其基因MspI多态性与心肌梗塞危险性的研究

目的;探讨凝血因子Ⅶ活性及其基因ＭｓｐＩ多态性与中国汉族人心肌梗塞的关系。 方法：测定１２５例健康人（正常对照组）和１３７例心肌梗塞患者（心肌梗塞组）血浆凝血因子Ⅶ活性;采用聚合酶链反应（ＰＣＲ）和ＭｓｐＩ酶切法确定其基因型。 结果：①心肌梗塞组血浆凝血因子Ⅶ活性（Ｐ＜０．０１）和血清总胆固醇（Ｐ＜０．０５）均显著高于正常对照组;仅前者与心肌梗塞的危险性独立相关（ＯＲ＝１．０４,Ｐ＜０．０１）。②凝血因子Ⅶ基因型和等位基因的频率分布在两组间无显著差异。③Ｍ_１Ｍ_１纯合子血浆凝血因子Ｗ活性显著高于Ｍ_１Ｍ_２杂合子（Ｐ＜０．０５）。 结论：支持血浆凝血因子Ⅶ活性升高是中国汉族人心肌梗塞的危险因素;凝血因子Ⅶ活性受其基因ＭｓｐＩ多态性的影响,但该多态性并不是中国汉族人心肌梗塞的独立危险因子。     

Coagulation factor VII and inflammatory markers in patients with coronary heart disease.

To further elucidate the connection between inflammation and factor VII (FVII) taking genetic variation in the FVII locus into account, we have examined 387 patients after myocardial infarction and 387 age-matched and sex-matched healthy control individuals. Circulating levels of C-reactive protein, FVII antigen (FVIIag), activated FVII (FVIIa), fibrinogen and interleukin-6 were analysed and all subjects were genotyped for the Arg353Gln polymorphism in the FVII locus. Plasma concentrations of C-reactive protein, fibrinogen, and interleukin-6 were higher among patients than control individuals. FVIIag was lower in the patient group, but for FVIIa there was no difference between the two groups. Among the inflammatory markers, only C-reactive protein indicated a weak nonlinear association with FVII. No significant difference in frequency of the Gln allele was observed between patients and control individuals but the presence of the Gln allele was associated with lower plasma levels of FVIIag and FVIIa in both groups. The low-grade chronic inflammation seen 3 months after myocardial infarction is not of major importance for the variation in plasma concentration of FVII. The presence of the Gln allele in the Arg353Gln polymorphism in the FVII locus did not differ between patients and control individuals but was associated with lower plasma levels of FVIIag and FVIIa that could have a protective effect against myocardial infarction. To further elucidate these facts, a prospective study should be performed to reduce the risk of a possible selection bias due to coronary heart disease death seen in retrospective case-control studies.     

冠心病患者胸腺苷合成酶多态性的探讨

目的研究胸腺苷合成酶(TS)5’-非翻译区(UTR)28bp串联重复序列多态性、3-’UTR1494bp位6bp插入或缺失多态性与血浆同型半胱氨酸(Hcy)水平及冠心病之间的关系。方法用多聚酶链式反应(PCR)方法检测122例冠心病患者(冠状动脉造影显示至少有一支血管狭窄≥50%)与56例对照组(冠状动脉造影未发现任何可辨认斑块或狭窄)的TS 5-’UTR 28bp串联重复序列多态性;用聚合酶链反应-限制性片段多态性(PCR-RFLP)分析3-’UTR1494bp位6bp插入或缺失多态性;用荧光衍生后高压液相色谱分离法检测血浆总Hcy水平。结果(1)冠心病组的血浆Hcy水平(12.99±4.76)μmol/L高于对照组(10.95±4.75)μmol/L(P=0.009)。(2)TS5-’UTR 28bp串联重复序列有三种基因型(3R/3R,3R/2R,2R/2R),这三种基因型频率在冠心病组和对照组之间的分布有差异(P=0.029);TS28各基因型个体的Hcy水平在冠心病组高于对照组(P=0.03)。3R/3R、3R/2R基因型个体的Hcy水平均高于2R/2R型个体(分别为P<0.001和P=0.011),但3R/3R基因型个体与3R/2R基因型个体的Hcy水平间的差异没有统计学意义(P=0.979)。(3)TS3-’UTR6bp插入或缺失多态性有三种基因型(+6bp/+6bp,+6bp/-6bp,-6bp/-6bp),这三种基因型频率在冠心病组和对照组之间的分布差异无显著性(P>0.05)。TS6各基因型个体的Hcy水平在冠心病组高于对照组(P=0.006)。冠心病组TS6 bp各基因型个体间Hcy水平的的差异均没有统计学意义(P均>0.05)。结论(1)高Hcy血症与冠心病有关系。(2)TS基因5-’UTR28bp串联重复序列多态性可能是冠心病发病中的一个遗传因素。3 R与冠心病组个体的Hcy水平有关系。     

凝因因子V多态性,活性与冠心病关系的研究

探讨凝血因子Ｖ（ＦＶ）与冠心病（ＣＨＤ）发病的关系。方法在１４１例ＣＨＤ和１４５例健康人作对照组,运用多聚酶链反应－变性梯度凝胶电泳技术（ＰＣＲ－ＤＧＧＥ）筛查ＦＶ基因全部外显子,随机对其中５５例ＣＨＤ和５５例健康人对照进行ＦＶ活性和ＡＦＰＣ抵抗（ＡＰＣＲ）的测定,并统计分析。     

Factor VII levels in patients undergoing coronary angiography: factor VII and coronary artery disease

BACKGROUND: Factor VII (F VII) has been widely investigated as a risk factor for coronary atherosclerosis, however there is still debate about its role in the progression of coronary artery disease (CAD). In this study F VII levels were measured in patients with angiographically proven CAD and its relation with disease severity, coronary events and with other risk factors of coronary atherosclerosis were examined. METHODS: Consecutive patients referred to coronary angiography were divided in three groups: 1. CAD group--those with a significant lesion in one or more coronary arteries (n = 155), 2. High-risk group--patients with normal coronary arteries and with two or more risk factors (n = 54), 3. Controls--patients with normal coronary arteries and with no or one risk factor (n = 90). CAD group was also studied according to the number of vessels involved and to the history of coronary events. RESULTS: Mean F VII levels were not different between the three groups of patients. In CAD group, F VII increased parallel to the number of vessels involved (one vessel disease: 85 +/- 20%, two vessel disease: 92 +/- 23%, three vessel disease: 105 +/- 23%). Patients with a history of coronary events had significantly higher F VII levels than those without such a history (96 +/- 25% versus 89 +/- 22% respectively, P = 0.02). However, logistic regression analysis revealed no significant relation between F VII and either the presence of CAD or coronary events. CONCLUSIONS: F VII levels increase in patients with previous coronary events, but it is not an independent risk factor for the progression or for the severity of CAD.     

Variation of the factor VII gene and ischemic heart disease in Japanese subjects

BACKGROUND: Polymorphisms of the 5' region (5'FT), an intronic mutation (IVS7), and the 353Arg-Gln (R353Q) substitution of the factor VII gene have been reported to be associated with the plasma level of factor VII. Greater than normal levels of factor VII have also been reported to be associated with atherothrombotic events. However, the significance of factor VII gene polymorphism in the pathogenesis of ischemic heart diseases (IHD) has not been confirmed. OBJECTIVE: To determine whether these three factor VII gene polymorphisms are associated with levels of factor VII in Japanese subjects, and whether these three polymorphisms of the factor VII gene are associated with the risk of myocardial infarction. METHODS: We studied three polymorphisms of the factor VII gene, 5'FT, IVS7, and R353Q polymorphisms, for 493 Japanese subjects consisting of 285 subjects without clinical evidence of ischemic heart disease (non-IHD group) and 208 myocardial infarction patients (myocardial infarction group). We also assessed the plasma levels of factor VII antigen (FVIIag) in 103 subjects in the non-IHD group. RESULTS: Multiple regression analysis revealed that the level of FVIIag was significantly associated with age, body mass index, cholesterol level and a polymorphism of the factor VII gene (5'FT). Logistic analysis of 493 subjects revealed that cholesterol level [P = 0.0036, odds ratio 1.010, 95% confidence interval (CI) 1.003-1.017], smoking (P = 0.0001, odds ratio 5.522, (95% CI 2.684-11.364) and diabetes mellitus (P = 0.0001, odds ratio 6.450, (95% CI 2.953-14.088) were risk factors for myocardial infarction. However, the three polymorphisms of factor VII gene were not associated with risk of myocardial infarction. CONCLUSION: The polymorphisms of the factor VII gene influenced the levels of factor VII but were not significantly associated with risk of myocardial infarction in Japanese subjects.     

Air pollution and markers of inflammation and coagulation in patients with coronary heart disease

RATIONALE: Ambient air pollution has been shown to be associated with cardiovascular morbidity and mortality. OBJECTIVES: A prospective panel study was conducted to study the early physiologic reactions characterized by blood biomarkers of inflammation, endothelial dysfunction, and coagulation in response to daily changes in air pollution in Erfurt, Germany. METHODS: Blood parameters were repeatedly measured in 57 male patients with coronary heart disease during the winter of 2000/2001. Fixed-effects linear and logistic regression models were applied, adjusting for trend, weekday, and meteorologic parameters. MEASUREMENTS: Hourly data on ultrafine particles (UFPs; number concentration of particles from 0.01 to 0.1 microm), mass concentration of particles less than 10 (PM(10)) and 2.5 microm in diameter, elemental and organic carbon, gaseous pollutants, and meteorologic data were collected at central monitoring sites. MAIN RESULTS: Increased levels of C-reactive protein above the 90th percentile were observed for an increase in air pollution concentrations of one interquartile range. The effect was strongest for accumulation mode particles, with a delay of 2 d (odds ratio [OR], 3.2; confidence interval [CI], 1.7, 6.0). Results were consistent for UFPs and PM(10), which also showed a 2-d delayed response (OR, 2.3; CI, 1.3, 3.8; and OR, 2.2; CI, 1.2, 3.8, respectively). However, not all of the blood markers of endothelial dysfunction and coagulation increased consistently in association with air pollutants. CONCLUSION: These results suggest that inflammation as well as parts of the coagulation pathway may contribute to the association between particulate air pollution and coronary events.     

老年冠心病患者血浆中肿瘤坏死因子及其基因多态性的研究

目的　对老年冠心病患者血浆肿瘤坏死因子 (TNF)水平及其基因多态性进行分析 ,探讨其在冠心病发病中的作用。方法　用ELISA及PCR法测定 40例冠心病患者及 30例健康对照者血浆TNF水平及TNF等位基因频率。结果　TNF等位基因频率分布 ,两组之间比较差异无显著性意义 (P >0 .0 5 ) ,而血浆中TNF水平 ,冠心病组明显高于对照组 ,两组之间比较差异有显著性意义 (P <0 .0 0 1) 。结论　TNF基因多态性在冠心病发病机理中可能不起重要作用。TNFA或TNFB基因多态性与冠心病患者血浆TNF水平升高没有关系。     

凝血因子Ⅴ和凝血因子Ⅷ活性的变化与冠心病的关系

目的：观察冠心病患者凝血因子活性的变化及其在冠心病发病中的作用。方法：用一期法(Onestage assay)测定58例冠心病患者血浆凝血因子Ⅴ活性(FⅤ：C)及凝血因子Ⅷ活性(FⅧ：C)、纤维蛋白原(Fg)含量，并与健康人上述指标进行比较，进行多因素回归分析。结果：急性心肌梗死、不稳定心绞痛患者较正常对照组FⅤ：C、FⅧ：C、Fg含量均明显增高，且急性心肌梗死患者与不稳定心绞痛患者之间Fg含量存在显著性差异。多因素回归分析中，FV：C、FⅧ：C进入回归方程。结论：凝血因子活性增高是引起冠心病患者血栓形成的重要因素。凝血系统活性增高在缺血性心脏病的发生、发展中起着重要作用，测定凝血因子Ⅴ及Ⅷ的活性及纤维蛋白原水平对探讨冠心病的发病机制及判断预后可能有一定的帮助。