The Role of β-Fibrinogen Genotype in Determining Plasma Fibrinogen Levels in Young Survivors of Myocardial Infarction and Healthy Controls from Sweden

Summary

β-fibrinogen G/A^-455 polymorphism genotype was determined in 123 young survivors of myocardial infarction and 86 healthy controls from Sweden. Frequency of the A^-455 allele was 0.25 (95% Confidence Interval 0.21–0.29) in both patients and controls, significantly higher than that reported previously (0.19, 95% Cl 0.16–0.22) in 292 men from the UK (1). Mean plasma fibrinogen level was significantly higher in patients (3.6 g/1) than in controls (3.1 g/1), with p <0.001. Genotype was significantly associated with (adjusted) plasma fibrinogen level in controls (p = 0.003). This effect was confined to the smokers (n = 50) where mean fibrinogen level was significantly (p = 0.001) higher in G/A^-455 and A/A^-455 individuals (3.5 g/1) compared with G/G^-455 homozygotes (2.9 g/1). There was a significant interaction between smoking status and genotype in determining plasma fibrinogen levels in the controls. These data provide independent confirmation of the association between β-fibrinogen G/A^-455 genotype and plasma fibrinogen levels previously observed in healthy men from the UK (1).

• References

• 1 Thomas AE, Green FR, Kelleher CH, Wilkes HC, Brennan PJ, Meade TW, Humphries SE. Variation in the promoter region of the β-fibrinogen gene is associated with plasma fibrinogen levels in smokers and non-smokers. Thromb Haemostas 1991; 65: 487-490
• 2 Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. New Engl J Med 1984; 311: 501-505
• 3 Stone MC, Thorp JM. Plasma fibrinogen – a major coronary risk factor. J Royal Coll Gen Prac 1985; 35: 565-569
• 4 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WRS, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease; principal results of the North wick Park Heart Study. Lancet 1986; ii: 533-537
• 5 Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease; the Framingham Study. J Amer Med Assoc 1987; 258: 1183-1186
• 6 Balleisen L, Schulte H, Assmann G, Epping P-H, van deLoo J. Coagulation factors and the progress of coronary heart disease. Lancet 1987; ii: 461
• 7 Broadhurst P, Kelleher C, Hughes L, Imeson JD, Raftery EB. Fibrinogen, factor VII clotting activity and coronary artery disease severity. Atherosclerosis 1990; 85: 169-173
• 8 Lowe GDO, Donnan PT, McColl P. et al. Blood viscosity, fibrinogen and activation of coagulation and leucocytes in peripheral arterial disease: Edinburgh Artery Study. Br J Haematol 1991; 77 (suppl): 27
• 9 Smith WCS, Woodward M, Tunstall-Pedoe H. Intermittent claudication in Scotland. In: Epidemiology of peripheral vascular disease. Fowkes FGR. (ed). London, UK: Springer-Verlag; 1992: 117-123
• 10 Kannel WB, D’Agostino RB. Update of fibrinogen as a major cardiovascular risk factor: the Framingham study. J Am Coll Cardiol 1990; 15: 156A
• 11 Banerjee AK, Pearson J, Gilliland EL, Goss D, Lewis JD, Stirling Y, Meade TW. A six year prospective study of fibrinogen and other risk factors associated with mortality in stable claudicants. Thromb Haemostas 1992; 68: 261-263
• 12 Wiseman S, Powell J, Greenhalg R, McCollum C, Kenchington G, Alexander C, Sian M, Franks P. The influence of smoking and plasma factors on prosthetic graft patency. Eur J Vase Surg 1990; 4: 57-61
• 13 Smith EB, Keen GA, Grant A. Fate of fibrinogen in human arterial intima. Arteriosclerosis 1990; 10: 263-275
• 14 Thompson WD, Smith EB, Stirk CM, Kochhar A. Atherosclerotic plaque growth; presence of stimulatory fibrin degradation products. Blood Coag Fibrinol 1990; 1: 489-493
• 15 Gurewich V, Lipinski B, Hyde F. The effect of the fibrinogen concentration and the leucocyte count on intravascular fibrin deposition from soluble fibrin monomer complexes. Thromb Haemostas 1976; 36: 605-614
• 16 Henschen A, McDonagh J. Fibrinogen, fibrin and factor XIII. In: Blood Coagulation. Zwaal RFA, Hemker HC. (eds). Amsterdam, the Netherlands: Elsevier Science Publishers BV (Biomedical Division); 1986: 171-239
• 17 Meade TW, Vickers MV, Thompson SG, Seghatchian MJ. The effects of physiological levels of fibrinogen on platelet aggregation. Thromb Res 1985; 38: 527-534
• 18 Marguerie G, Ginsberg MH, Plow EF. The role of fibrinogen in platelet aggregation. In: Fibrinogen-Fibrin Formation and Fibrinolysis Vol. 4. Lane DA, Henschen A, Jasani MK. (eds). Berlin, Germany: Walter de Gruyter; 1986: 175-183
• 19 Lowe GDO, Forbes CD. Blood rheology and thrombosis. Clin Lab Haematol 1981; 10: 343-367
• 20 Meade TW, North WRS, Chakrabarti R, Haines AP, Stirling Y. Population-based distributions of haemostatic variables. Br Med Bull 1977; 33: 283-288
• 21 Markowe HLJ, Marmot MG, Shipley MJ. et al. Fibrinogen: a possible link between social class and coronary heart disease. Br Med J 1985; 291: 1312-1314
• 22 Kannel WB, D’Agostino RB, Belanger AJ. Fibrinogen, cigarette smoking and risk of cardiovascular disease: insights from Framingham Study. Am Heart J 1987; 113: 1006-1010
• 23 Rosengren A, Wilhelmsen L, Welin L, Tsipogianni A, Teger-Nilsson AC, Wedel H. Social influences and cardiovascular risk factors as determinants of plasma fibrinogen concentration in a general population sample of middle-aged men. Br Med J 1990; 300: 634-638
• 24 Lee AJ, Smith WCS, Lowe GDO, Tunstall-Pedoe H. Plasma fibrinogen and coronary risk factors: Scottish Heart Health Study. J Clin Epidemiol 1990; 43: 913-919
• 25 Yarnell JWG, Fehily AM, Milbank J, Rubiki AJ, Eastham R, Hayes TRM. Determinants of plasma lipoproteins and coagulation factors in men from Caerphilly, South Wales. J Epidemiol Commun Health 1983; 37: 137-140
• 26 Meade TW, Imeson J, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease. Lancet 1987; ii: 986-988
• 27 Abbott RD, Yin Yin, Reed DM, Yano K. Risk of stroke in male cigarette smokers. New Engl J Med 1986; 315: 717-720
• 28 The Health Consequences of Smoking. In: Cardiovascular disease. Report of the Surgeon General. Washington, DC: US Dept Health and Human Services; 1983. p 319
• 29 Folsom AR, Wu KK, Davis CE, Conlan MG, Sorlie PD, Szklo M. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors. Atherosclerosis 1991; 91: 191-205
• 30 Krobot K, Hense HW, Cremer P, Eberle E, Keil U. Determinants of plasma fibrinogen: relation to body weight, waist-to-hip ratio, smoking, alcohol, age and sex. Arteriosclerosis Thromb 1992; 12: 780-788
• 31 Green GK, Heady A, Oliver MF. Blood pressure, cigarette smoking and heart attack in the WHO co-operative trial of clofibrate. Int J Epidemiol 1989; 18: 355-360
• 32 Meade TW, Brozovic M, Chakrabarti R, Howarth DJ, North WRS, Stirling Y. An epidemiological study of the haemostatic and other effects of oral contraceptives. Br J Haematol 1976; 34: 353-364
• 33 Fuller JH, Keen H, Jarrett RJ. et al. Haemostatic variables associated with diabetes and its complications. Br Med J 1979; ii: 964-966
• 34 Balleisen L, Bailey J, Epping PH, Schulte H, van deLoo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population; I Baseline data on the relation to age, gender, body-weight, smoking, alcohol, pill-using and menopause. Thromb Haemostas 1985; 315: 717-720
• 35 Meade TW, Chakrabarti R, Haines AP, North WRS, Stirling Y. Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations. Br Med J 1979; 1: 153-156
• 36 O’Brien JR, Etherington MD, Jamieson S, Sussex J. The effect of ICI 55,897 and clofibrate on platelet function and other tests abnormal in atherosclerosis. Thromb Haemostas 1978; 40: 75-82
• 37 Pickart L, Thaler MM. Suppression of tumor-associated hyperfibrinogenemia and free fatty acidemia with p-phenoxybenzalbutyrate (clofibrate). Cancer Res 1979; 39: 3845-3848
• 38 Andersen P, Smith P, Seljeflot I, Brataker S, Arnesen H. Effects of gemfibrozil on lipids and haemostasis after myocardial infarction. Thromb Haemostas 1990; 63: 174-177
• 39 Olaisen B, Teisberg P, Gedde-Dahl Jr T. Fibrinogen γ chain locus is on chromosome 4 in man. Hum Genet 1982; 61: 24-26
• 40 Humphries SE, Imam AMA, Robbins TP, Cook M, Carritt B, Ingle C, Williamson R. The identification of a DNA polymorphism of the a fibrinogen gene, and the regional assignment of the human fibrinogen genes to 4q26-qter. Hum Genet 1984; 68: 148-153
• 41 Kant JA, Fornace Jr AJ, Saxe D, Simon MI, McBride OW, Crabtree GR. Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion. Proc Natl Acad Sci USA 1985; 82: 2344-2348
• 42 Fey GH, Fuller GM. Regulation of acute phase gene expression by inflammatory mediators. Mol Biol Med 1987; 4: 323-338
• 43 Ritchie DG, Levy BA, Adams MA, Fuller GM. Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway. Proc Natl Acad Sci USA 1982; 79: 1530-1534
• 44 Birch HE, Schreiber G. Transcriptional regulation of plasma protein synthesis during inflammation. J Biol Chem 1986; 261: 8077-8080
• 45 Fuller GM, Otto JM, Woloski BM, McGary CT, Adams MA. The effects of hepatocyte stimulating factor on fibrinogen biosynthesis in hepatocyte monolayers. J Cell Biol 1985; 101: 1481-1486
• 46 Huber P, Laurent M, Dalmon J. Human β-fibrinogen gene expression. Upstream sequences involved in its tissue specific expression and its dexamethasone and interleukin 6 stimulation. J Biol Chem 1990; 265: 5695-5701
• 47 Hamsten A, de FaireU, Iselius L, Blomback M. Genetic and cultural inheritance of plasma fibrinogen concentration. Lancet 1987; ii: 988-991
• 48 Berg K, Kierulf P. DNA polymorphisms at fibrinogen loci and plasma fibrinogen concentration. Clin Genet 1989; 36: 229-235
• 49 Humphries SE, Cook M, Dubowitz M, Stirling Y, Meade TW. Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations. Lancet 1987; i: 1452-1455
• 50 Connor JM, Fowkes FGR, Wood J, Smith FB, Donnan PT, Lowe GDO. Genetic variation at fibrinogen loci and plasma fibrinogen levels. J Med Genet 1992; 29: 480-482
• 51 Thompson SG, Martin JC, Meade TW. Sources of variability in coagulation factor assays. Thromb Haemostas 1987; 58: 1073-1077
• 52 Fowkes FGR, Connor JM, Smith FB, Wood J, Donnan PT, Lowe GDO. Fibrinogen genotype and risk of peripheral atherosclerosis. Lancet 1992; 339: 693-696
• 53 Hamsten A, Blomback M, Wiman B, Svensson J, Szamosi A, de Faire U, Mettinger L. Haemostatic function in myocardial infarction. Br Heart J 1986; 55: 58-66
• 54 Vermylen C, de VrekerRA, Verstraete M. A rapid enzymatic method for assay of fibrinogen fibrin polymerisation time (FPT). Clin Chim Acta 1963; 8: 418-424
• 55 Laurel CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 1966; 15: 45-52
• 56 Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OH, Beg WR, Jones HW, Rary JM. Analysis of human Y-chromosome specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 1977; 74: 1245-1249
• 57 Colton T. Inference on Proportions. In: Statistics in Medicine. Boston, USA: Pub: Little, Brown and Company Inc.; 1974. pp 151-188
• 58 Yu S, Sher B, Kudryk B, Redman CM. Intracellular assembly of human fibrinogen. J Biol Chem 1983; 258: 13407-13410
• 59 Roy SN, Mukhopadhyay G, Redman CM. Regulation of fibrinogen assembly. Transfection of HepG2 cells with Bβ cDNA specifically enhances synthesis of the three component chains of fibrinogen. J Biol Chem 1990; 265: 6389-6393
• 60 Dalmon J, Laurent M, Courtois G. The human β fibrinogen promoter contains a hepatocyte nuclear factor 1-dependent interleukin-6 responsive element. Mol Cell Biol 1993; 13: 1183-1193