Relationship between β-fibrinogen promoter -455G/A (HaeⅢ) polymorphism and plasma fibrinogen of the patients with ischemic cerebrovascular disease

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Journal Title:
Volume 2, Issue 04, 2003
Key Word:
ischemic cerebrovascular disease;β-Fibrinogen Gene;plasma Fibrinogen

Abstract: Objective The -455G/A (HaeⅢ) polymorphism of the β-fibrinogen gene influences levels of plasma fibrinogen.We determined whether it influences risk ofischemic cerebrovascular disease. Methods We accumulated 134 acute ischemiccerebrovascular disease (ICVD) cases and compared their -455G/A status with that in a control group (n=166). Furthermore,we analysed the β-fibrinogen gene -455A/G polymorphism for all subjects by PCR-RFLP with the restrictive enzyme HaeⅢ.Results Plasma fibrinogen was higher in AA homozygous participants (341 mg/dL) than in persons carrying the G allele: GA(290 mg/dL), GG (298 mg/dL) in the control group. Plasma fibrinogen was also higher in AA homozygous patients (353mg/dL) than in cases carrying the G allele: GA (287 mg/dL), GG (302 mg/dL) in the ICVD group. However, -455G/Apolymorphism of the β-fibrinogen gene was found not to be significantly associated with ICVD. Conclusion Although aminor effect on plasma fibrinogen cannot be excluded, -455G/A polymorphism of the β-fibrinogen gene does not appear tobe an important genetic determinant of ICVD.

  • [1]Folsom AR, Wu KK, Rosamond WD, et al. Prospective study of hemostatic factors and incidence of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) Study[J ]. Circulation,1997, 96:1102-1108.
  • [2]Danesh J, Collins R, Appleby P, et al. Association offibrinogen, Creactive protein, albumin, or leukocyte count with coronary heart disease: Meta-analyses of prospective studies [J ]. JAMA, 1998,279:1477-1482.
  • [3]Thomas A, Lamlum H, Humphries S, et al. Green, Linkage disequilibrium across the fibrinogen locus as shown by five genetic polymorphisms, G/A-455 (HAEⅢ), C/T148 (HindⅢ/AluI), T/G+1689(AvaⅢ), and Bcll (β-Fibrinogen) and TaqI (β-Fibrinogen), and their detection by PCR[J]. Human Mutation, 1994, 3: 79-81.
  • [4]van der Bom JG, de Maat MPM, Bots ML, et al. Elevated plasma fibrinogen. Cause or consequence of cardiovascular disease? [J].Arterioscler Thromb Vasc Biol, 1998, 18:621-625.
  • [5]Tybjaerg-Hansen A, Agerholm-Larsen B, Humphries SE, et al. A common mutation (G-455(A) in the β-fibrinogen promoter is an independent predictor of plasma fibrinogen, but not ofischemic heart disease. A study of 9,127 individuals based on the Copenhagen City Heart Study[J]. J Clin Invest, 1997, 99: 3034-3039.
  • [6]Connor JM, Fowkes FGR, Wood J, et al. Genetic variation at fibrinogen loci and plasma fibrinogen levels[J]. J Med Genet, 1992,29: 480-482.
  • [7]Carter AM, Mansfield MW, Stickland MH, et al. β-fibrinogen gene-455G/A polymorphism and fibrinogen levels. Risk factors for coronary artery disease in subjects with NIDDM [J]. Diabetes Care,1996, 19: 1265-1268.
  • [8]Green F, Hamsten A, Blomback M, et al. The role of β-fibrinogen genotype in determining plasma fibrinogen levels in young survivors of myocardial infarction and healthy controls from Sweden [J]. Thromb Haemost, 1993, 70: 915-920.
  • [9]Scarabin PY, Bara L, Ricard S, et al. Genetic variation at the βfibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study [J]. Arterioscler Thromb, 1993, 13: 886-891.
  • [10]Behague l, Pokier O, Nicaud V, et al. β-fibrinogen gene polymorphisms are associated with plasma fibrinogen and coronary artery disease in patients with myocardial infarction [J]. The ECTIM Study, Circulation, 1996, 93: 440-449.
  • [11]Nishiuma S, Kario K, Yakushijin K, et al. Genetic variation in the promoter region of the beta-fibrinogen gene is associated with ischaemic stroke in a Japanese population [J]. Blood Coagul Fibrinolysis, 1998, 9: 373-379.
  • [12]Thomas AE, Green FR, Kelleher CH, et al. Variation in the promoter region of the β-fibrinogen gene is associated with plasma fibrinogen levels in smokers and non-smokers [J]. Thromb Haemost, 1991,65: 487-490.
  • [13]Kain K, Catto AJ, Young J, et al. Increased fibrinogen, von Willebrand factor and tissue plasminogen activator levels in insulin resistant South Asian patients with ischaemic stroke [J]. Atherosclerosis,2002, 163: 371-376.
  • [14]Brown ET, Fuller GM. Detection of a complex that associates with the β-fibrinogen G-455-A polymorphism [J]. Blood, 1998, 92:3286-3293.
  • [15]Maresca G, Di Blasio A, Marchioli R, et al. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update[J]. Arterioscler Thromb Vasc Biol, 1999, 19:1368-1377.
  • [16]Margaglione M, Di Minno G, Grandone E, et al. Raised plasma fibrinogen concentrations in subjects attending a metabolic wardrelation to family history and vascular risk factors [J]. Thromb Haemost, 1995, 73: 579-583.
  • [17]Liu Y, Pan JQ, Wang SJ, et al. β-fibrinogen gene -455A/G polymorphism and plasma fibrinogen level in Chinese stroke patients[J]. Chin Med J, 2002, 115(2): 214-216.
  • [18]Doggen C J, Bertina RM, Cats VM, et al. Fibrinogen polymorphisms are not associated with the risk of myocardial infarction [J]. Br J Haematol, 2000, 110: 935-938.
  • [19]Nascetti S, Elosua R, Pena A, et al. Variables associated with fibrinogen in a population-based study: interaction between smoking and age on fibrinogen concentration [J]. European Journal of Epidemiology, 2001, 17: 953-958.
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