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Association of β-fibrinogen gene 148C/T and 455G/A polymorphisms and coronary artery disease in Chinese population: A Meta analysis
XiaoChao Chen,MingTong Xu,LiZi Jin,Jian Chen,WeiQing Chen
Science China Life Sciences , 2008, DOI: 10.1007/s11427-008-0102-0
Abstract: The purpose of our study was to evaluate the correlation between the β-fibrinogen gene 148C/T and 455G/A polymorphisms and susceptibility to coronary artery disease in the Chinese population using a meta-analytic approach. Eligible studies about this correlation were identified by searching the PubMed, EMBASE, and CNKI databases. Of the 13 identified, 7 (with 1488 cases and 1234 controls) involved the 148C/T polymorphism and 9 (with 1023 cases and 1081 controls) involved the 455G/A polymorphism. No publication bias was detectable and heterogeneity testing found significant differences between the ORs for both groups of studies. The combined OR for the 7 studies on susceptibility to coronary artery disease in 148T allele carriers compared to the 148C/C wild-type homozygotes was 1.31 (95%CI: 0.94–1.84, P=0.11). The combined OR for the 9 studies on susceptibility to coronary artery disease in 455A allele carriers compared to the 455G/G wild-type homozygotes was 1.75 (95%CI: 1.24–2.46, P=0.001). Our results suggest the absence of an association between the β-fibrinogen gene 148C/T polymorphism and susceptibility to coronary artery disease and the possibility that 455G/A polymorphism (in particular, allele A) increases susceptibility to this disease in the Chinese population.
中国汉人纤维蛋白原β链基因-148C/T, -455G/A多态性与冠心病关系的Meta分析
中国科学 生命科学 , 2008,
Abstract: 有关中国汉人纤维蛋白原b链基因多态性与冠心病关系的研究屡见报道, 但不同的研究之间结果存在一定的差异. 本研究根据相应的入选条件, 通过文献检索收集中国汉人纤维蛋白原b链基因-148C/T, 455G/A多态性与冠心病关系的病例-对照研究, 剔除不符合要求的文献, 对入选文献进行一致性检验并根据检验结果进行数据合并荟萃(Meta)分析, 计算总OR值. 共13篇文献符合要求纳入研究, 其中7篇关于-148C/T多态性研究包括1488例冠心病患者和1234例对照人群, 9篇关于-455G/A多态性的研究包括1023名患者和1081名对照者, 入选研究无明显发表偏倚, 入选研究的同质性检验显示各研究结果间存在明显的异质性, 数据合并结果显示-148C/T多态性位点C/T+T/T比C/C的OR值为1.31, 95%CI为0.94~1.84(P=0.11), -455G/A多态性位点G/A+A/A比G/G的OR值为1.75, 95%CI为1.24~2.46(P=0.001). 本研究的初步结果显示纤维蛋白原b链基因-455G/A多态性与中国汉人冠心病易感性相关, -455A等位基因可能是冠心病的遗传易感基因, -148C/T基因多态性与中国汉人冠心病易感性无明显关系.
中国汉人纤维蛋白原β链基因-148C/T,-455G/A多态性与冠心病关系的Meta分析  [PDF]
中国科学 生命科学 , 2008,
Abstract: 有关中国汉人纤维蛋白原b链基因多态性与冠心病关系的研究屡见报道,但不同的研究之间结果存在一定的差异.本研究根据相应的入选条件,通过文献检索收集中国汉人纤维蛋白原b链基因-148C/T,455G/A多态性与冠心病关系的病例-对照研究,剔除不符合要求的文献,对入选文献进行一致性检验并根据检验结果进行数据合并荟萃(Meta)分析,计算总OR值.共13篇文献符合要求纳入研究,其中7篇关于-148C/T多态性研究包括1488例冠心病患者和1234例对照人群,9篇关于-455G/A多态性的研究包括1023名患者和1081名对照者,入选研究无明显发表偏倚,入选研究的同质性检验显示各研究结果间存在明显的异质性,数据合并结果显示-148C/T多态性位点C/T+T/T比C/C的OR值为1.31,95%CI为0.94~1.84(P=0.11),-455G/A多态性位点G/A+A/A比G/G的OR值为1.75,95%CI为1.24~2.46(P=0.001).本研究的初步结果显示纤维蛋白原b链基因-455G/A多态性与中国汉人冠心病易感性相关,-455A等位基因可能是冠心病的遗传易感基因,-148C/T基因多态性与中国汉人冠心病易感性无明显关系.
Role of Genetic Changes in the Progression of Cardiovascular Diseases  [cached]
S. A. Sheweita,H. Baghdadi,A. R. Allam
International Journal of Biomedical Science , 2011,
Abstract: This review aims to investigate the role of genetic changes in the development of cardiovascular diseases [CVD]. Oxidation of Low density Lipoprotein (LDL) and mutations in LDLreceptors gene are a trigger for numerous of atherogenic events. Also, endothelial nitric oxide synthase (eNOS) plays an important role in vasodilatation of blood vessels through synthesis of nitric oxide.Three single base pair changes, 786T/C, 922A/G, and 1468T/A, have been identified in the promoter region of the eNOS gene and are associated with coronary spasm. Moreover, two distinct variable nucleotide tandem repeats (VNTRs) in introns 4 and 13 have been detected. The presence of a minimum of 38 CA repeats in intron 13 has been associated with an independent 2.2-fold increase in the risk of coronary artery disease [CAD]. Plasma glutathione peroxidase (GPx-3) maintains the vascular bioavailability of nitric oxide (NO), through depletion of reactive oxygen species. Mutation(s) or polymorphism(s) in the plasma GPx-3 gene promoter may predispose to a thrombotic disorder, and constitute a genetic risk factor for thrombotic cerebrovascular disease. Hyperhomocysteinemia is another independent risk factor for atherosclerosis and arterial thrombosis. Severe hyperhomocysteinemia could be caused by cystathionine-β-synthase enzyme deficiency but it could be due to homozygosity of a common 677C/T point mutation in the coding region of the methylenetetrahydrofolate reductase (MTHFR) gene as a 3-fold increase in risk of CAD is associated with the MTHFR 677TT genotype. A second common variant in MTHFR 1298A/C is associated with decreased enzyme activity in vitro and in vivo, especially when occurring simultaneously with the 677 C/T polymorphism. Elevated fibrinogen, an essential component of the coagulation system, has been most consistently associated with arterial thrombotic disorders. Several polymorphisms (148C/T, 455G/A, and -854G/A) have been identified in the genes encoding the 3 pairs of fibrinogen polypeptide chains. The -455G/A, and -854G/A substitutions are the most physiologically relevant mutations. In addition the -455A allele has been associated with the progression of atheroma, and also with a 2.5-fold increase in risk of multiple lacunar infarcts in a cohort of elderly patients with stroke. It is concluded that genetic changes in the previously mentioned genes could play a significant role in the initiation and progression of CVD. This review provides useful information for both physicians and medical students whom are interested in human genetics which is related to cardiova
Combined Effect of Hemostatic Gene Polymorphisms and the Risk of Myocardial Infarction in Patients with Advanced Coronary Atherosclerosis  [PDF]
Nicola Martinelli, Elisabetta Trabetti, Mirko Pinotti, Oliviero Olivieri, Marco Sandri, Simonetta Friso, Francesca Pizzolo, Claudia Bozzini, Pier Paolo Caruso, Ugo Cavallari, Suzanne Cheng, Pier Franco Pignatti, Francesco Bernardi, Roberto Corrocher, Domenico Girelli
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001523
Abstract: Background Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI. Methodology/Principal Findings We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen β -455G>A, FV Leiden and “R2”, FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (χ2 for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (≤2) alleles had a decreased MI risk (OR 0.34, 95%CIs 0.13–0.93), while those with more (≥8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03–6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential. Conclusions The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD.
The correlation study of beta-fibrinogen gene polymorphisms and plasma fibrinogen concentration in patients with colorectal cancer

王静文,韩 韬,陈 玺,
WANG Jingwen
, HAN Tao, CHEN Xi, et al

- , 2015, DOI: 10.3969/j.issn.1007-3969.2015.10.009
Abstract: 背景与目的:结直肠癌患者病程中常伴有血浆纤维蛋白原(fibrinogen,Fg)浓度的升高。该研究探讨结直肠癌人群中FGBβ基因-448G/A、-148C/T、-1420G/A、-854G/A的单核苷酸多态性(single nucleotide polymorphism,SNP)频率分布和血浆Fg浓度的关系,分析其对肿瘤发生、发展的影响。方法:采集194例结直肠癌患者和74例健康者外周血,用实时荧光定量多聚酶链反应(real-time fluorescence quantitative PCR,RTFQ-PCR)法分析FGBβ基因频率分布,用Clauss凝固法检测血浆Fg浓度。结果:结直肠癌转移组和无转移组的血浆Fg浓度均较对照组显著升高(P<0.05)。疾病组中FGBβ-148T等位基因频率和突变型基因频率均显著高于对照组(P<0.05)。各组人群中FGBβ-148T携带者的血浆Fg浓度均明显高于非携带者(P<0.05)。在Ⅳ期患者中FGBβ-148C/T突变型者中位PFS较野生型者差异无统计学意义(P>0.05)。结论:结直肠癌患者体内Fg浓度升高,提示其可能参与恶性肿瘤发生、发展的过程。FGBβ-148C/T位点的SNP是导致血浆Fg浓度改变的原因之一,但与Ⅳ期患者的预后无关。
Fibrinogen beta variants confer protection against coronary artery disease in a Greek case-control study
Eirini V Theodoraki, Tiit Nikopensius, Julia Suhorut?enko, Vassileios Peppes, Panagiota Fili, Genovefa Kolovou, Vassileios Papamikos, Dimitrios Richter, Nikolaos Zakopoulos, Kaarel Krjut?kov, Andres Metspalu, George V Dedoussis
BMC Medical Genetics , 2010, DOI: 10.1186/1471-2350-11-28
Abstract: We genotyped for rs2070022, rs2070016, rs2070006 in FGA gene, the rs7673587, rs1800789, rs1800790, rs1800788, rs1800787, rs4681 and rs4220 in FGB gene and for the rs1118823, rs1800792 and rs2066865 SNPs in FGG gene applying an arrayed primer extension-based genotyping method (APEX-2) in a sample of CAD patients (n = 305) and controls (n = 305). Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), before and after adjustment for potential confounders.None of the FGA and FGG SNPs and FGA, FGB, FGG and FGA-FGG haplotypes was associated with disease occurrence after adjustment. Nevertheless, rs1800787 and rs1800789 SNPs in FGB gene seem to decrease the risk of CAD, even after adjustment for potential confounders (OR = 0.42, 95%CI: 0.19-0.90, p = 0.026 and OR = 0.44, 95%CI:0.21-0.94, p = 0.039, respectively).FGA and FGG SNPs as well as FGA, FGB, FGG and FGA-FGG haplotypes do not seem to be important contributors to CAD occurrence in our sample. On the contrary, FGB rs1800787 and rs1800789 SNPs seem to confer protection to disease onset lowering the risk by about 50% in homozygotes for the minor alleles.Fibrinogen (Factor I) constitutes a water-soluble glycoprotein with a molecular weight of 340 kDa that is mainly synthesized in hepatocytes. It is a major factor of the coagulation system that participates in the process of hemostasis in two discrete pathways: Primarily, it is part of the final common pathway of the coagulation cascade. Secondarily, fibrinogen is bound to platelet GpIIb/IIIa membrane receptors and forms a web that provides stability to the newly-formed thrombus [1,2]. Apart from its role in coagulation reactions, fibrinogen participates in atherosclerosis development by promoting the adhesion of platelets and white blood cells to the endothelial surface [3-5] by promoting muscle cell proliferation and migration, as well as by modulating the binding of plasmin with its receptor [1]. Fibrinogen levels in pl
Risk factors, biochemical markers, and genetic polymorphisms in early coronary artery disease
Izar, Maria Cristina;Fonseca, Francisco Antonio Helfenstein;Ihara, Sílvia Saiuli Miki;Kasinski, Nelson;Sang, Won Han;Lopes, Ieda Edite Lanzarini;Pinto, Leonor do Espírito Santo de Almeida;Relvas, Waldir Gabriel Miranda;Louren?o, Daisy;Tufik, Sérgio;Paola, Angelo Amato Vincenzo de;Carvalho, Antonio Carlos Camargo;
Arquivos Brasileiros de Cardiologia , 2003, DOI: 10.1590/S0066-782X2003000400003
Abstract: objective: to assess the risk factors, lipid and apolipoprotein profile, hemostasis variables, and polymorphisms of the apolipoprotein ai-ciii gene in early coronary artery disease (cad). methods: case-control study with 112 patients in each group controlled by sex and age. after clinical evaluation and nutritional instruction, blood samples were collected for biochemical assays and genetic study. results: familial history of early cad (64 vs 39%), arterial hypertension (69 vs 36%), diabetes mellitus (25 vs 3%), and previous smoking (71 vs 46%) were more prevalent in the case group (p<0.001). hypertension and diabetes were independent risk factors. early cad was characterized by higher serum levels of total cholesterol (235 ± 6 vs 209 ± 4 mg/dl), of ldl-c (154 ± 5 vs 135 ± 4 mg/dl), triglycerides (205 ± 12 vs 143 ± 9 mg/dl), and apolipoprotein b (129 ± 3 vs 105 ± 3 mg/dl), and lower serum levels of hdl-c (40 ± 1 vs 46 ± 1 mg/dl) and apolipoprotein ai (134 ± 2 vs 146 ± 2mg/dl) [p<0.01], in addition to an elevation in fibrinogen and d-dimer (p<0.02). the simultaneous presence of the rare alleles of the apo ai-ciii genes in early cad are associated with hypertriglyceridemia (p=0.03). conclusion: of the classical risk factors, hypertension and diabetes mellitus were independently associated with early cad. in addition to an unfavorable lipid profile, an increase in the thrombotic risk was identified in this population. an additive effect of the apo ai-ciii genes was observed in triglyceride levels.
Assessment of Diagnostic Efficiency of Lipoprotein (a), Homocysteine, High Sensitive C-Reactive Protein and Fibrinogen in Patients with Coronary Artery Disease  [cached]
Ebru Dundar Yenilmez,Hale Toyaksi,Abdi Bozkurt,Abdullah Tuli
Cukurova Medical Journal , 2013,
Abstract: Backround: To evaluate the diagnostic value of major and other risk factors as lipoprotein (Lp) (a), homocysteine (Hcy), high sensitive C-reactive protein (hs-CRP) and fibrinogen in CAD patients. Methods: A total of 223 subjects (118 patients and 105 controls) were included in the study according to their coronary angiographic results. Lipoprotein (a), Hcy, hs-CRP and fibrinogen levels were measured using immunoturbidometric, florescent polarization immunoassay and nefelometric methods, respectively. Fasting glucose and lipid parameters, except low density lipoprotein cholesterol (LDL-C), are determined by enzymatic colorimetric methods and the LDL-C levels were calculated by the Fridewald formula. Results: Logistic regression analysis showed that when the biochemical variables in placed in a model, the most important variables were Lp (a), Hcy, hs-CRP and fibrinogen. We showed that each unit of Lp (a), Hcy, hs-CRP and fibrinogen increases the risk of CAD 1.029, 1.177, 1.027 and 1.013 fold, respectively. Among these, fibrinogen level was the most sensitive and efficient parameter in prediction of CAD. Conclusion: Although Lp (a), Hcy, hs-CRP and fibrinogen are independent risk factors for CAD, fibrinogen was the most important one. Fibrinogen can be used as a reliable risk factor for CAD in clinical practice. [Cukurova Med J 2013; 38(4.000): 559-566]
Prothrombotic polymorphisms and long-term prognosis of patients with stable ischemic heart disease (Full english text)  [cached]
A.L. Komarov,O.O. Shahmatova,D.V. Rebrikov,D.Yu. Trophimov
Rational Pharmacotherapy in Cardiology , 2011,
Abstract: Aim. To estimate influence of thrombosis associated genetic factors on cardiovascular complications (CVC) occurrence in patients with stable ischemic heart disease (IHD) on the base of 5-year prospective survey.Material and methods. A total of 503 patients with the mean age of 59.4 years were enrolled into the study. The follow-up period was 5.4 years. Composite endpoint included the following cases of fatal and nonfatal CVC: death, acute coronary syndrome, ischemic stroke/transient ischemic attack, peripheral arterial thrombosis and revascularization of affected vascular system. We determined prevalence and prognostic value of mutations and polymorphisms in genes that encode blood clotting factors (factor V Leiden G1691A, prothrombin G20210A, -fibrinogen 455G> A), platelet GPIIIa receptor (C1565T) and enzymes involved in homocysteine metabolism (methylentetrahydrofolate reductase (C667 T MTHFR) and A1298C, methionine synthase (MTR) A2756G, methionine synthase-reductase (MTRR) A66G and transcobalamin (TCN) C776G).Results. Overall incidence rate of vascular events made up 31.0%. MTHFR and TCN polymorphisms proved to be significant in regard to cardiovascular risk among all studied genetic indices. Carriage of at least C667 T one MTHFR polymorphic allele increased risk of CVC 1.64 times (95% confidence interval (CI) 1.2-2.3, p=0.003). Homozygous carriage of MTHFR 1298 AА and TCN 776 СС “wild” genotypes increased risk of CVC 1.63 times (95% CI 1.2-2.3, р=0.006) and 1.37 times (95% CI 1.001-1.89, р=0.04), respectively. Such genetic variants as MTHFR C667 T/СТ and 1298 AА impacted prognosis only given concomitant decrease in plasma folate level, which was observed in 56.1% of the patients.Conclusion. It can be recommended to test the presence of MTHFR C667 T, MTHFR 1298 AА and TCN 776 СС, and to simultaneously assess folate level in IHD patients in order to clarify risk of unfavorable cardiovascular events.
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