Plasma fibrinogen concentration predicts the risk of myocardial infarction differently in various parts of Europe: effects of β-fibrinogen genotype and environmental factors

Maria Nastase Mannila; Angela Silveira; Emma Hawe; Per Eriksson; Marie Françoise Aillaud; Irene Juhan-Vague; John Yudkin; Maurizio Margaglione; Giovanni di Minno; Luciana Mussoni; Elena Tremoli; Steve Humphries; Anders Hamsten; the HIFMECH study group; on-behalf-of

doi:10.1160/TH04-06-0339

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2004; 92(06): 1240-1249
DOI: 10.1160/TH04-06-0339

Theme Issue Article

Schattauer GmbH

Plasma fibrinogen concentration predicts the risk of myocardial infarction differently in various parts of Europe: effects of β-fibrinogen genotype and environmental factors

The HIFMECH Study

Maria Nastase Mannila

¹Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

,

Angela Silveira

¹Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

,

Emma Hawe

²Centre for Cardiovascular Genetics, Department of Medicine, Royal Free and University College London Medical School, London, UK

,

Per Eriksson

¹Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

,

Marie Françoise Aillaud

³Laboratoire d’Hématologie, CHU Timone, Marseille, France

,

Irene Juhan-Vague

³Laboratoire d’Hématologie, CHU Timone, Marseille, France

,

John Yudkin

⁴Diabetes and Cardiovascular Disease Academic Unit, Department of Medicine, University College London, London, UK

,

Maurizio Margaglione

⁵Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

,

Giovanni di Minno

⁵Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

,

Luciana Mussoni

⁶Department of Pharmacological Sciences, University of Milan, and Monzino Cardiological Centre, IRCCS, Milan, Italy

,

Elena Tremoli

⁶Department of Pharmacological Sciences, University of Milan, and Monzino Cardiological Centre, IRCCS, Milan, Italy

,

Steve Humphries

²Centre for Cardiovascular Genetics, Department of Medicine, Royal Free and University College London Medical School, London, UK

,

Anders Hamsten

¹Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

,

the HIFMECH study group

› Institutsangaben

Abstract

Summary

The propensity to atherothrombotic disease differs in Europe, with high-risk regions located in the North of Europe and lowrisk regions in the South of Europe. The HIFMECH study (Hypercoagulability and Impaired Fibrinolytic function MECHanisms predisposing to myocardial infarction (MI) study) was undertaken to elucidate genetic and environmental mechanisms underlying MI based on investigations of postinfarction patients and healthy individuals recruited from Stockholm, Sweden, London, England (North of Europe), Marseille, France and San Giovanni Rotondo, Italy (South of Europe). In the present report, emphasis was placed on fibrinogen, a multifunctional protein, widely recognized as an independent predictor of atherothrombotic disease. The adjusted plasma fibrinogen concentration was an independent discriminator between cases and controls in London (SOR 3.58; 95% CI 1.31; 9.83), but not in the other centres. Genotyping for six β-fibrinogen promoter single nucleotide polymorphisms was performed of which -249C/T, -455G/A and -854G/A were used in analysis as a consequence of the linkage disequilibrium pattern. Four haplotypes, with similar distribution across Europe, were detected: CGG (46.7%), CAG (20.3%), TGG (18.2%) and CGA (14.8%). A significant haplotype effect on plasma fibrinogen concentration was observed in patients (p <0.001) but not in controls (p = 0.08).The -455G/A genotype related to plasma fibrinogen concentration amongst patients along with centre and IL-6 concentration (together explaining 11.5% of the variation), whereas predictors amongst controls included centre, body mass index, IL-6 and smoking habit (explaining 15.7%). Thus, plasma fibrinogen concentration contributes differently to MI across Europe, and a disease-related stimulus is required to evoke allele-specific regulation of fibrinogen synthesis.

Keywords

Fibrinogen - myocardial infarction - SNPs - haplotype

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Referenzen

References
1 Meade TW, Mellows S, Brozovic M. et al. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 02: 533-7.
2 Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. Ann Intern Med 1993; 118: 956-63.
3 Folsom AR, Rosamond WD, Shahar E. et al. Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation 1999; 100: 736-42.
4 Palmieri V, Celentano A, Roman MJ. et al. Relation of fibrinogen to cardiovascular events is independent of preclinical cardiovascular disease: the Strong Heart Study. Am Heart J 2003; 145: 467-74.
5 Yarnell JW, Sweetnam PM, Rumley A. et al. Lifestyle and hemostatic risk factors for ischemic heart disease: the Caerphilly Study. Arterioscler Thromb Vasc Biol 2000; 20: 2719.
6 Hamsten A, Iselius L, de Faire U. et al. Genetic and cultural inheritance of plasma fibrinogen concentration. Lancet 1987; 02: 988-91.
7 Friedlander Y, Elkana Y, Sinnreich R. et al. Genetic and environmental sources of fibrinogen variability in Israeli families: the Kibbutzim Family Study. Am J Hum Genet 1995; 56: 1194-206.
8 de Lange M, Snieder H, Ariens RA. et al. The genetics of haemostasis: a twin study. Lancet 2001; 357: 101-5.
9 Kant JA, Fornace Jr. AJ, Saxe D. et al. Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion. Proc Natl Acad Sci U S A 1985; 82: 2344-8.
10 Roy SN, Mukhopadhyay G, Redman CM. Regulation of fibrinogen assembly. Transfection of Hep G2 cells with B beta cDNA specifically enhances synthesis of the three component chains of fibrinogen. J Biol Chem 1990; 265: 6389-93.
11 Roy S, Overton O, Redman C. Overexpression of any fibrinogen chain by Hep G2 cells specifically elevates the expression of the other two chains. J Biol Chem 1994; 269: 691-5.
12 Yu S, Sher B, Kudryk B. et al. Intracellular assembly of human fibrinogen. J Biol Chem 1983; 258: 13407-10.
13 Humphries SE, Cook M, Dubowitz M. et al. Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations. Lancet 1987; 01: 1452-5.
14 Green F, Hamsten A, Blomback M. et al. The role of beta-fibrinogen genotype in determining plasma fibrinogen levels in young survivors of myocardial infarction and healthy controls from Sweden. Thromb Haemost 1993; 70: 915-20.
15 Tybjaerg-Hansen A, Agerholm-Larsen B, Humphries SE. 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. J Clin Invest 1997; 99: 3034-9.
16 Behague I, Poirier O, Nicaud V. 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. Circulation 1996; 93: 440-9.
17 de Maat MP, Kastelein JJ, Jukema JW. et al. -455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: proposed role for an acute-phase reaction pattern of fibrinogen. REGRESS group. Arterioscler Thromb Vasc Biol 1998; 18: 265-71.
18 Simmonds RE, Hermida J, Rezende SM. et al. Haemostatic genetic risk factors in arterial thrombosis. Thromb Haemost 2001; 86: 374-85.
19 Juhan-Vague I, Morange PE, Frere C. et al. The plasminogen activator inhibitor-1 -675 4G/5G genotype influences the risk of myocardial infarction associated with elevated plasma proinsulin and insulin concentrations in men from Europe: the HIFMECH Study. J Thromb Haemost 2003; 01: 2322-9.
20 Mohamed-Ali V, Gould MM, Gillies S. et al. Association of proinsulin-like molecules with lipids and fibrinogen in non-diabetic subjects—evidence against a modulating role for insulin. Diabetologia 1995; 38: 1110-6.
21 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-46.
22 de Maat MP, Pijl H, Kluft C. et al. Consumption of black and green tea had no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals. Eur J Clin Nutr 2000; 54: 757-63.
23 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
24 Chakravarti A, Buetow KH, Antonarakis SE. et al. Nonuniform recombination within the human beta-globin gene cluster. Am J Hum Genet 1984; 36: 1239-58.
25 Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001; 68: 978-89.
26 Levi F, Lucchini F, Negri E. et al. Trends in mortality from cardiovascular and cerebrovascular diseases in Europe and other areas of the world. Heart 2002; 88: 119-24.
27 Keys A. Coronary heart disease-the global picture. Atherosclerosis 1975; 22: 149-92.
28 Meade TW, North WR, Chakrabarti R. et al. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1980; 01: 1050-4.
29 Maresca G, Di Blasio A, Marchioli R. et al. Measuring plasma fibrinogen to predict stroke and myocardial infarction: An update. Arterioscler Thromb Vasc Biol 1999; 19: 1368-77.
30 Ma J, Hennekens CH, Ridker PM. et al. A prospective study of fibrinogen and risk of myocardial infarction in the Physicians’ Health Study. J Am Coll Cardiol 1999; 33: 1347-52.
31 Dalmon J, Laurent M, Courtois G. The human beta fibrinogen promoter contains a hepatocyte nuclear factor 1-dependent interleukin-6-responsive element. Mol Cell Biol 1993; 13: 1183-93.
32 van ’t Hooft FM, von Bahr SJ, Silveira A. et al. Two common, functional polymorphisms in the promoter region of the beta-fibrinogen gene contribute to regulation of plasma fibrinogen concentration. Arterioscler Thromb Vasc Biol 1999; 19: 3063-70.
33 Doggen CJ, Bertina RM, Cats VM. et al. Fibrinogen polymorphisms are not associated with the risk of myocardial infarction. Br J Haematol 2000; 110: 935-8.
34 Leander K, Wiman B, Hallqvist J. et al. The G-455A polymorphism of the fibrinogen Bbeta-gene relates to plasma fibrinogen in male cases, but does not interact with environmental factors in causing myocardial infarction in either men or women. J Intern Med 2002; 252: 332-41.
35 de Maat MP, Bladbjerg EM, Drivsholm T. et al. Inflammation, thrombosis and atherosclerosis: results of the Glostrup study. J Thromb Haemost 2003; 01: 950-7.
36 Kerlin B, Cooley BC, Isermann BH. et al. Cause-effect relation between hyperfibrinogenemia and vascular disease. Blood 2004; 103: 1728-34.
37 Lim BC, Ariens RA, Carter AM. et al. Genetic regulation of fibrin structure and function: complex gene-environment interactions may modulate vascular risk. Lancet 2003; 361: 1424-31.
38 Fatah K, Hamsten A, Blomback B. et al. Fibrin gel network characteristics and coronary heart disease: relations to plasma fibrinogen concentration, acute phase protein, serum lipoproteins and coronary atherosclerosis. Thromb Haemost 1992; 68: 130-5.
39 Fatah K, Silveira A, Tornvall P. et al. Proneness to formation of tight and rigid fibrin gel structures in men with myocardial infarction at a young age. Thromb Haemost 1996; 76: 535-40.
40 Collet JP, Soria J, Mirshahi M. et al. Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure. Blood 1993; 82: 2462-9.
41 Reid DD, Hamilton PJ, McCartney P. et al. Smoking and other risk factors for coronary heart-disease in British civil servants. Lancet 1976; 02: 979-84.
42 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; 02: 986-8.
43 Hunter KA, Garlick PJ, Broom I. et al. Effects of smoking and abstention from smoking on fibrinogen synthesis in humans. Clin Sci 2001; 100: 459-65.
44 Tuut M, Hense HW. Smoking, other risk factors and fibrinogen levels: Evidence of effect modification. Ann Epidemiol 2001; 11: 232-8.