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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
1   Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
,
Angela Silveira
1   Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
,
Emma Hawe
2   Centre for Cardiovascular Genetics, Department of Medicine, Royal Free and University College London Medical School, London, UK
,
Per Eriksson
1   Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
,
Marie Françoise Aillaud
3   Laboratoire d’Hématologie, CHU Timone, Marseille, France
,
Irene Juhan-Vague
3   Laboratoire d’Hématologie, CHU Timone, Marseille, France
,
John Yudkin
4   Diabetes and Cardiovascular Disease Academic Unit, Department of Medicine, University College London, London, UK
,
Maurizio Margaglione
5   Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
,
Giovanni di Minno
5   Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
,
Luciana Mussoni
6   Department of Pharmacological Sciences, University of Milan, and Monzino Cardiological Centre, IRCCS, Milan, Italy
,
Elena Tremoli
6   Department of Pharmacological Sciences, University of Milan, and Monzino Cardiological Centre, IRCCS, Milan, Italy
,
Steve Humphries
2   Centre for Cardiovascular Genetics, Department of Medicine, Royal Free and University College London Medical School, London, UK
,
Anders Hamsten
1   Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
,
the HIFMECH study group › Author AffiliationsFinancial support: The HIFMECH study was supported by grants from the European Commission (BMH-4-CT96-0272), the Swedish Medical Research Council, the Swedish Heart-Lung Foundation, the British Heart Foundation (RG 2000015 and PG/99153), INSERM and Université de la Méditerranée (EPI 9936), Fondation pour la Recherche Médicale (FRM) and Programme Hospitalier de Recherche Clinique (PHRC 1996).
Further Information

Publication History

Received 02 June 2004

Accepted after resubmission 27 August 2004

Publication Date:
02 December 2017 (online)

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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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