宁夏回族和汉族老年急性冠状动脉综合征患者凝血因子Ⅶ基因多态性的分布特征

目的探讨血浆凝血因子Ⅶ(FⅦ)基因多态性在宁夏回、汉族老年急性冠状动脉综合征(ACS)患者中的分布特征。方法选择冠心病患者664例分为回族冠心病组(336例)和汉族冠心痛组(328例),其中回族ACS患者194例,汉族ACS患者175例;同期选择健康体检者750例分为回族对照组(400倒)和汉族对照组(350例),采用候选基因及病例对照研究的方法,以聚合酶链反应-限制性片段长度多态性技术,行FⅦ基因的R353Q、-3230/10hp和HVR4基因多态性分析,同时采用重组可溶性组织因子法测定血浆FⅦa水平。结果回、汉族冠心痛组患者的血浆FⅦa水平均显著高于同族对照组(P<0.01)。R353Q基因型及等位基因频率分布在回族冠心痛组与回族对照组差异有统计学意义(P<0.01),-323 0/10 bp基因型及等位基因频率分布在汉族冠心痛组与汉族对照组差异有统计学意义(P<0.01)。回族ACS患者Q/Q+R/Q基因型频率高于回族非ACS患者,差异有统计学意义(P<0.01)。结论宁夏回、汉族人群中存在FⅦ基因多态性;Q等位基因可能是回族人群ACS发生的遗传保护因子,FⅦa水平受R353Q基因多态性影响。     

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。     

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.     

凝血因子Ⅶ水平及其基因多态性与 PTE 的相关研究简

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（P〉0.05）.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.     

河南汉族人群凝血因子Ⅶ基因的多态性与冠心病的相关性研究

目的探讨河南汉族人群凝血因子Ⅶ(FⅦ)基因R353Q、5'F7多态性与冠心病的关系.方法利用多聚酶链反应限制性内切酶片段长度多态性(PCR-RFLP)技术,检测419例冠心病(组)患者和564例对照(组)者FⅦ基因R353Q、5'F7多态性.结果R353Q多态性的基因型频率分布在两组间差异无统计学意义,5'F7多态性的频率分布在两组间差异有统计学意义,二者联合分析在两组间差异具有统计学意义.多元Logistic回归分析结果显示二者均与冠心病发病无相关性.结论在河南汉族人群中,基因11353Q可能不足以构成冠心病发生的独立遗传危险因子,携带P10等位基因可能是冠心病的一个遗传保护因子.二者联合突变对冠心病可能有保护性.     

唐山地区汉族人群凝血因子Ⅶ基因多态性与急性缺血性脑卒中的关系研究

目的探究唐山地区汉族人群凝血因子Ⅶ(FⅦ)基因多态性与急性缺血性脑卒中的关系。方法选取2009年10月—2011年5月在河北联合大学附属医院急诊科住院的72例急性缺血性脑卒中患者作为观察组,另选取2009年10月—2011年10月在河北联合大学附属医院体检的健康者88例作为对照组。采用基因测序方法检测FⅦ基因R353Q(rs6046)位点多态性。比较两组受试者基因型和等位基因分布频率。结果两组受试者年龄、性别、吸烟率、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、血糖(GLU)比较,差异均无统计学意义(P0.05)。基因测序见FⅦ基因扩增片段存在R353Q(rs6046)位点碱基转换突变(G→A),并发现2种基因型:纯合子RR,杂合子RQ。两组受试者FⅦ基因R353Q(rs6046)位点RR、RQ基因型及R、Q等位基因分布频率比较,差异无统计学意义(P0.05)。结论唐山地区汉族人群FⅦ基因多态性与急性缺血性脑卒中无关。     

冠心病患者与正常人凝血因子Ⅶ基因多态性的研究

目的：探讨中国汉族人群中凝血因子Ⅶ基因R353Q、HVR4多态性的分布及其与冠心病和心肌梗死的关系。方法：利用聚合酶链反应和限制性内切酶片段长度多态性核苷酸分型技术，检测234例冠心病患和105名正常对照的凝血因子Ⅶ基因型，并结合选择性冠状动脉造影结果进行分析。结果：基因型频率符合Hardy-Weinberg平衡定律。凝血功能指标凝血酶原时间、部分凝血活酶时间、凝血酶时间不受凝血因子Ⅶ基因多态性的影响。R353Q和HVR4基因多态性与冠心病和狭窄血管支数之间比较差异均无显性。R353Q基因型频率和等位基因频率在非心肌梗死组和心肌梗死组比较有明显差异（χ^2=4.711,P＜0．05，OR＝0．37，95％CI 0．15－0．94），而VR4基因多态性在两组间比较无统计学意义（χ^2=0.142,P＞0．05）。结论：汉族人群中存在凝血因子Ⅶ基因的R353Q和HVR4多态性，其中Q等位基因可能是心肌梗死的遗传保护因子。     

冠心病患者凝血因子Ⅶ启动子区域5′F7基因多态性的研究

利用聚合酶链反应-限制性内切酶片段长度多态性分析技术检测564例健康人(对照组)和419例冠心病(CHD)患者(CHD组)的凝血因子Ⅶ(FⅦ)启动子区域的基因型。结果CHD组5′F 7多态性的基因型(0 bp纯合子393例,0 bp/10 bp杂合子+10 bp纯合子26例)与对照组(0 bp纯合子507例,0 bp/10 bp杂合子+10 bp纯合子57例)间差异具有统计学意义(P<0.05);且两组间等位基因频率的差异亦具有统计学意义。提示汉族人群中CHD患者存在FⅦ基因的5′F 7多态性,其中10 bp等位基因可能是冠心病的遗传保护因子。     

凝血因子基因多态性与深静脉血栓形成的相关性探讨

目的探讨凝血因子基因多态性与深静脉血栓形成（DVT）的相关性。方法采用PCR-RFLP法对103例DVT患者（观察组）和250例健康人（对照组）进行FⅡ／G20210A、FⅦ／R353Q、F／Val34LeuFⅦ基因多态性检测,并对基因型频率与等位基因频率作对比分析。结果观察组与对照组FⅡ／G20210A、FⅦ／R353Q、F ／Val34Leu的基因型频率及等位基因频率差异无统计学意义,三种基因型频率的分布均符合Hardy-Weinberg平衡定律。结论FⅡ／G20210A、FⅦ／R353Q基因多态性可能不是深静脉血栓形成发病的遗传学风险因子;F／Val34Leu多态性可能不是深静脉血栓形成发病的遗传保护因子。三种基因多态性均存在种族和地域差异。     

华南汉族脑出血患者凝血因子ⅦR353Q基因型的检测

目的观察凝血因子ⅦR353Q基因多态性在华南汉族人群中的分布及其与脑出血的关系。方法应用聚合酶链反应和限制性内切酶片长多态性技术检测了36例脑出血患者和按年龄、性别、体重、职业、吸烟史、胆固醇、甘油三酯和血糖等因素与脑出血患者配对的36例正常对照者的凝血因子ⅦR353Q基因型,探讨脑出血的发生与因子ⅦR353Q基因型的关系。结果凝血因子ⅦR353Q基因型有RR、RQ和QQ三种,这三种基因型在对照组的分布频率分别是80.5%、16.7%和2.8%;在脑出血组为80.5%和19.5%,未检测到QQ基因型。等位基因R和Q基因频率在在对照组为88.9%和11.1%,在脑出血组为90.3%和9.7%。基因型频率符合Hardy-Weinberg平衡定律。R353Q基因型频率和等位基因频率在脑出血组和对照组之间比较差异均无显著性。结论没有发现凝血因子ⅦR353Q基因多态性与华南汉族脑出血的发生有明显关系。     

Influence of Age, Sex and Blood Groups on 15 Blood Coagulation Laboratory Variables in a Reference Material Composed of 80 Blood Donors

Abstract. 15 blood coagulation and fibrinolysis variables were determined in 80 healthy blood donors. Males were shown to have significantly higher levels of factor VII and factor X, and in subjects with blood group O significantly lower levels of VIIIR:AG were observed. In individuals with blood group O a skewed distribution of VIIIR:AG suggested a mixed population of this antigenic determinant. No significant correlation (r<0.36) was found between age and any of the laboratory variables.     

Association of depressive symptoms with coagulation factors in young healthy individuals

BACKGROUND: Depression has been reported to be an independent risk factor for coronary heart disease (CHD). We investigated the association of depressive symptoms with lipids and coagulation factors in young individuals free of CHD. METHODS: We recruited 1073 young healthy individuals candidates for military academies (mean age=18.4+/-0.8 years, males 762) in whom the presence of depressive symptoms was assessed by using the depression scale of Minnesota Multiphasic Personality Inventory test. Total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein (a), fibrinogen, factors VII, VIII and X were measured. RESULTS: The depression score ranged from 22 to 90. The participants were divided into quartiles according to the depression score. Three hundred twenty-two subjects were classified in the upper quartile (score>48) and 269 in the lower quartile (score<37) of the depression score. Factor VII (102.95+/-24 versus 98.5+/-20%) and X levels (92+/-11 versus 89.7+/-10%) were significantly higher in individuals in the upper quartile compared to the lower quartile of the depression score. In a logistic regression model with factor VII as dependent variable (upper versus lower quartile) and depression score, age, gender, body mass index, exercise and smoking as predictor variables, depression was an independent predictor of factor VII levels with an adjusted odds ratio for high levels of factor VII of 1.05 (95% confidence interval 1.008-1.09, p=0.01). Factor VII levels were associated with triglycerides (r=0.21, p=0.001) while factor X with triglycerides (r=0.22, p<0.001) and cholesterol levels (r=0.12, p<0.001). CONCLUSIONS: Depressed mood is associated with a hypercoagulant profile as it is expressed by the higher levels of coagulation factors VII and X. This might partially explain the higher propensity for CHD of people with depressive symptoms.     

Postprandial triglycerides and blood coagulation.

Most of our lifetime we spend in the postprandial state. Postprandial triglyceridemia may represent a procoagulant state involving disturbances of both blood coagulation and fibrinolysis, in particular due to elevation of the plasma levels of activated factor VII (VIIa) and plasminogen activator inhibitor (PAI-1). Therefore, disturbances of the hemostatic system might, at least partly, account for by the link between hypertriglyceridemia and coronary heart disease (CHD). Factor VIIa is the first enzyme of the blood coagulation system and serves a priming function for triggering of the clotting cascade. The coagulant activity of factor VII (VIIc, total activity of factor VII in plasma) was identified as an independent predictor of myocardial infarction in initially healthy middle-aged men, and particularly of fatal coronary events, and both serum cholesterol and triglyceride concentrations correlated positively with the VIIc level. Addition of fat to diet has been consistently shown to cause a rapid conversion of the factor VII zymogen into its active form (VIIa) whereas the concentration of total protein is unaffected. Postprandial activation of factor VII is dependent on lipolytic activity and it is mainly supported by large triglyceride-rich lipoprotein of the VLDL class. Studies in vivo with specific coagulation factor-deficient patients indicate that factor IX is essential for the postprandial activation of factor VII. The basal generation of thrombin seems to be unaffected by increased plasma levels of VIIa. However, since VIIa-tissue factor complex is responsible for the initiation of the coagulation cascade, increased generation of VIIa in the postprandial state would increase the potential for thrombin production in the event of plaque rupture. Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of the plasminogen activators in the circulation and thereby the principal inhibitor of the fibrinolytic system. Postprandial triglyceridemia has been observed in many, not all, studies to increase PAI-1 plasma levels, which would further strengthen the chances of thrombotic occlusion of a vessel after rupture of an atherosclerotic plaque.     

内皮型一氧化氮合酶基因G894T多态性与宁夏回、汉族原发性高血压的关系

目的:研究宁夏地区回、汉族原发性高血压(EH)人群与内皮型一氧化氮合酶(eNOS)基因G894T多态性之间的关系。方法:收集宁夏回族142例EH患者(回EH组)、112例正常血压者(回对照组)及宁夏汉族158例EH患者(汉EH组)、176例正常血压者(汉对照组),应用PCR-RFLP技术进行eNOS G894T基因多态性的检测,统计分析该位点不同基因型及等位基因频率在两族人群中的分布。结果:回EH组与回对照组,汉EH组与汉对照组,回、汉EH组间与回、汉对照组间基因型及等位基因频率差异无统计学意义。结论:eNOS基因G894T多态性与宁夏地区回、汉族人群EH发病无关;该位点多态性在宁夏回、汉族人群之间无种族差异性。     

Frequencies of mild factor V, VII and X deficiencies in a Japanese population.

We investigated the frequencies of coagulation factor deficiencies in a Japanese population. We measured factor II, V, VII and X activity in 100 healthy individuals. A specific factor deficiency was determined according to the factor activity and the ratio of the factor activity to that of other coagulation factors. Seven samples showed factor activity less than the mean -2SD of standardized factor activity (factor II: three; factor V: one; factor VII: one; factor X: one and factor V+factor VII: one). The samples with low factor II and factor VII activity were determined not to be due to deficiency because the ratios of these factor activities to other factor activities were within the range of the mean +/- 2SD. We measured activity ratios in the remaining 97 samples and identified one sample with factor V deficiency and two with factor VII deficiency. Thus, six samples with coagulation factor deficiency were identified (factor X: one; factor V: two; factor VII: two and factor V + factor VII: one). These results suggest that the Japanese population has relatively high frequencies of mild factor V, factor VII and factor X deficiencies, in which activity is reduced to approximately 50% (36-64%) of normal plasma.     

Increased fibrinogen and factor VII activity levels in patients after myocardial infarction]

Functional and biochemical parameters of the haemostatic system in coronary heart disease (CHD) are still not well defined. Epidemiological studies indicate a positive correlation between fibrinogen (F) level and cardiovascular morbidity and mortality. Two independent ways of factor VII activation in the coagulation cascade suggest a special role of this factor in clot forming (Fig. 1). 22 patients (pts) under 55 yrs with a history of myocardial infarction (MT) and 22 healthy control men were studied for F level and factor VII activity (fVIIa). We found increased F level (M-363.3 mg/dl) and high level of VIIa (M-150.3%) in plasma of pts with a history of MI. Furthermore a strong positive correlation between fVIIa in plasma and F level (r = 0.62), serum cholesterol (chol) (r = 0.35), serum triglycerides (tg) (r = 0.32) (Tab. 2) was bound. Calculations were performed for all subjects: pts and control combined in one group. A possible influence of diet on fVIIa level is discussed. One should consider the usefulness of oral anticoagulants in the prophylaxis of MT.     

凝血指标在判断肝硬化患者病变严重程度中的价值

目的探讨凝血指标诊断乙型肝炎肝硬化病变严重程度的临床价值。方法收集乙型肝炎肝硬化患者58例,健康对照者20例。采用凝固法检测凝血酶原时间活动度(PTA)、活化部分凝血活酶时间及凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ的活性,发色底物法检测抗凝血酶Ⅲ(ATⅢ),同时检测常规生化指标。结果PTA、Ⅱ、Ⅶ、ATⅢ在肝硬化ChildPughA、B、C间两两比较差异均有统计学意义(P<001)。接受者操作特征曲线分析当PTA、Ⅶ分别以64%、50%为诊断ChildPughB的界值时,曲线下面积分别为0689、0610,敏感度分别为769%、615%,特异度分别为622%、556%;以54%、39%为诊断ChildPughC的界值时,AUC分别为0924、0942,敏感度分别达800%、867%,特异度分别达884%、907%。将凝血指标、生化指标与ChildPugh分数进行多元逐步线性回归,得到Y=15008-0018×PTA-0288×胆碱酯酶 0264×胆红素-0988×白蛋白-0034×Ⅶ,R2=0871。将Y<8的患者划分为“a”级,8~10为“b”级,>10为“c”级,诊断准确率达845%。结论Ⅶ因子是有助于判断肝硬化病变严重程度的指标。     

Factor VII and haemostasis

The role of factor VII in the haemostatic mechanism as well as thrombosis has recently gained new interest. Today's concept that factor VII may be a key regulator in the initiation of blood coagulation is based on studies that provide new evidence for a mandatory activation of factor VII to factor VIIa in blood. Exposure of thromboplastin to the circulation may not trigger activation of blood coagulation before the one chain factor VII is converted to the active two chain form of factor VIIa. A hypothetical model is proposed for the initiation and subsequent activation steps of the blood coagulation process. In this model, it is suggested that circulating activators of factor VII activate inactive complexes of thromboplastin-factor VII. Subsequently, newly generated factor Xa will accelerate this reaction and thereafter be the most potent activator of factor VII. This model would also fit with the clinical observation that moderate factor VII deficiency may be associated with thrombotic episodes discussed in this communication. This article also discusses the role of recombinant factor VIIa in the treatment of factor VIII deficiency patients with acquired factor VIII inhibitors, factor VII and ischemic heart disease and the factor VII-phospholipid complex, and the regulation of the thromboplastin-factor VIIa complex by factor Xa and extrinsic pathway inhibitor (EPI).     

Prognostic analysis and comparison of colon cancer in Han and Hui patients

AIM:To investigate the relevant prognostic factors and their differences between colorectal cancer(CRC)patients of Chinese Han and Hui ethnicities in the Beijing region.METHODS:A retrospective analysis of 880 patients diagnosed with CRC at Xuanwu Hospital,Capital Medical University between September 2001 and September2011 was performed.Among the 880 patients,398 and482 were Hui and Han,respectively.Characteristics including sex,age,diet,tumor size,primary tumor site,Dukes’stage and degree of differentiation were analyzed for their influence on prognosis.Data on dietary structures were recorded through a questionnaire survey conducted during the patient’s first visit,return visit or follow-up checkups.RESULTS:Among patients with colon cancer,the5-year survival rate for patients of Hui ethnicity was lower than that for Han patients(P=0.025).Six risk factors(age of onset,dietary structure,tumor size,Dukes’stage,location of cancer and degree of differentiation)in both Han and Hui patients were identified as prognostic factors(P<0.05).Multivariate analysis showed that age of onset(P=0.002),diet(P=0.000),Dukes’stage(P=0.000)and degree of differentiation(P=0.000)are prognostic factors affecting both ethnic groups.Comparison of prognostic factors between Han and Hui patients with CRC showed that dietary structure was a statistically significant factor,and diet varied significantly between the two ethnic groups.CONCLUSION:Dietary structure has a significant influence on colon cancer prognosis among Han and Hui patients with colon cancer in Beijing,which may cause a difference in their survival rates.