β-Fibrinogen gene -455G/A polymorphism and coronary heart disease incidence: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract PURPOSE: The −455G/A (HaeIII) polymorphism of the β-fibrinogen gene influences levels of plasma fibrinogen. We determined whether it influences risk of coronary heart disease. METHODS: We conducted a case-cohort study nested within a prospective investigation, the Atherosclerosis Risk in Communities Study. We accumulated 398 incident coronary heart disease cases over a median of 5.3 years of follow-up and compared their −455G/A status with a random sample of the cohort n = 498 . RESULTS: Plasma fibrinogen was higher p = 0.04 in AA homozygous participants (341 mg/dL) than in persons carrying the G allele: GA (290 mg/dL), GG (298 mg/dL). However, there was no significant association between −455G/A and incident CHD. CONCLUSIONS: Although a small effect cannot be excluded, −455G/A does not appear to be an important genetic determinant of CHD.

[1]  A. Clauss,et al.  Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens , 1957 .

[2]  S. Humphries,et al.  Variation in the Promoter Region of the β Fibrinogen Gene Is Associated with Plasma Fibrinogen Levels in Smokers and Non-Smokers , 1991, Thrombosis and Haemostasis.

[3]  T. Meade,et al.  HAEMOSTATIC FUNCTION AND ISCHAEMIC HEART DISEASE , 1981, The Lancet.

[4]  A. Evans,et al.  Genetic variation at the beta-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[5]  R. D'Agostino,et al.  Fibrinogen and risk of cardiovascular disease. The Framingham Study. , 1987, JAMA.

[6]  A. Hofman,et al.  Elevated plasma fibrinogen: cause or consequence of cardiovascular disease? , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[7]  G. Assmann,et al.  Impact of polymorphisms in the alpha- and beta-fibrinogen gene on plasma fibrinogen concentrations of coronary heart disease patients. , 1995, Thrombosis research.

[8]  S. Humphries,et al.  Association of genetic variation at the β‐fibrinogen gene locus and plasma fibrinogen evels; interaction between allele frequency of the G/A‐455polymorphism, age and smoking , 1996, Clinical genetics.

[9]  S. Humphries,et al.  A common mutation (G-455--> A) in the beta-fibrinogen promoter is an independent predictor of plasma fibrinogen, but not of ischemic heart disease. A study of 9,127 individuals based on the Copenhagen City Heart Study. , 1997, Journal of Clinical Investigation.

[10]  A. Folsom,et al.  Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. , 1997, Circulation.

[11]  A. Folsom,et al.  Polymorphisms of the Beta Fibrinogen Gene and Plasma Fibrinogen Concentration in Caucasian and Japanese Population Samples , 1995, Thrombosis and Haemostasis.

[12]  W. Gruber,et al.  Reagent for the Enzymatic Determination of Serum Total Triglycerides with Improved Lipolytic Efficiency , 1984, Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie.

[13]  P. Donnan,et al.  Genetic variation at fibrinogen loci and plasma fibrinogen levels. , 1992, Journal of medical genetics.

[14]  S. Thompson,et al.  HAEMOSTATIC FUNCTION AND ISCHAEMIC HEART DISEASE: PRINCIPAL RESULTS OF THE NORTHWICK PARK HEART STUDY , 1986, The Lancet.

[15]  A. Carter,et al.  β-fibrinogen gene −455 G/A Polymorphism and Fibrinogen Levels: Risk factors for coronary artery disease in subjects with NIDDM , 1996, Diabetes Care.

[16]  V. Nguyen.  Fibrinogen and risk of cardiovascular disease: Kannel WB, Wolf PA, Castelli WP, et al JAMA 258: 1183–1186 Sep 1987 , 1988 .

[17]  Ronald J. Prineas,et al.  The Minnesota code manual of electrocardiographic findings : standards and procedures for measurement and classification , 1982 .

[18]  L. Wilhelmsen,et al.  Fibrinogen as a risk factor for stroke and myocardial infarction. , 1984, The New England journal of medicine.

[19]  P. Talmud,et al.  European Atherosclerosis Research Study: genotype at the fibrinogen locus (G-455-A beta-gene) is associated with differences in plasma fibrinogen levels in young men and women from different regions in Europe. Evidence for gender-genotype-environment interaction. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[20]  G. Lowe,et al.  Fibrinogen, Factor VII and PAI-1 Genotypes and the Risk of Coronary and Peripheral Atherosclerosis: Edinburgh Artery Study , 1999, Thrombosis and Haemostasis.

[21]  L. Chambless,et al.  High‐Resolution B‐Mode Ultrasound Reading Methods in the Atherosclerosis Risk in Communities (ARIC) Cohort , 1991, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[22]  George Howard,et al.  High‐resolution B‐Mode Ultrasound Scanning Methods in the Atherosclerosis Risk in Communities Study (ARIC) , 1991, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[23]  Aric Invest.  The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators , 1989 .

[24]  R Peto,et al.  Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. , 1998, JAMA.

[25]  M. Blombäck,et al.  The Role of β-Fibrinogen Genotype in Determining Plasma Fibrinogen Levels in Young Survivors of Myocardial Infarction and Healthy Controls from Sweden , 1993, Thrombosis and Haemostasis.

[26]  D. Arveiler,et al.  Beta fibrinogen gene polymorphisms are associated with plasma fibrinogen and coronary artery disease in patients with myocardial infarction. The ECTIM Study. Etude Cas-Temoins sur l'Infarctus du Myocarde. , 1996, Circulation.

[27]  A. Zwinderman,et al.  −455G/A Polymorphism of the β-Fibrinogen Gene is Associated With the Progression of Coronary Atherosclerosis in Symptomatic Men , 1998 .

[28]  Oxon Dm.  Obituary. Rupert Samuel Bruce Pearson. , 1974 .

[29]  A. Folsom,et al.  Community surveillance of coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) Study: methods and initial two years' experience. , 1996, Journal of clinical epidemiology.

[30]  A. Folsom,et al.  Differences between respondents and nonrespondents in a multicenter community-based study vary by gender and ethnicity , 1996 .

[31]  F. Green,et al.  Linkage disequilibrium across the fibrinogen locus as shown by five genetic polymorphisms, G/A −455 (HaeIII), C/T −148 (HindIII/AluI), T/G+1689 (AvaII), and BclI (β‐fibrinogen) and TaqI (α‐fibrinogen), and their detection by PCR , 1994 .

[32]  W. Barlow,et al.  Robust variance estimation for the case-cohort design. , 1994, Biometrics.

[33]  A. Evans,et al.  β Fibrinogen Gene Polymorphisms Are Associated With Plasma Fibrinogen and Coronary Artery Disease in Patients With Myocardial Infarction , 1996 .

[34]  A. Gardemann,et al.  Positive Association of the β Fibrinogen H1/H2 Gene Variation to Basal Fibrinogen Levels and to the Increase in Fibrinogen Concentration during Acute Phase Reaction but not to Coronary Artery Disease and Myocardial Infarction , 1997, Thrombosis and Haemostasis.

[35]  L. Iacoviello,et al.  Bcl I polymorphism in the fibrinogen beta-chain gene is associated with the risk of familial myocardial infarction by increasing plasma fibrinogen levels. A case-control study in a sample of GISSI-2 patients. , 1997, Arteriosclerosis, Thrombosis and Vascular Biology.

[36]  J. Ziegenhorn,et al.  Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency. , 1983, Clinical chemistry.

[37]  P. Donnan,et al.  Fibrinogen genotype and risk of peripheral atherosclerosis , 1992, The Lancet.

[38]  G. Fuller,et al.  Detection of a complex that associates with the Bbeta fibrinogen G-455-A polymorphism. , 1998, Blood.