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Thromb Haemost 2006; 95(03): 420-427
DOI: 10.1160/TH05-11-0777
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Epistatic and pleiotropic effects of polymorphisms in the fibrinogen and coagulation factor XIII genes on plasma fibrinogen concentration, fibrin gel structure and risk of myocardial infarction

Maria Nastase Mannila
1   Atherosclerosis Research Unit, King GustafV Research Institute, Karolinska Institutet, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
,
Per Eriksson
1   Atherosclerosis Research Unit, King GustafV Research Institute, Karolinska Institutet, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
,
Carl-Göran Ericsson
2   Department of Medicine, Cardiology Unit, Danderyd Hospital, Stockholm, Sweden
,
Anders Hamsten
1   Atherosclerosis Research Unit, King GustafV Research Institute, Karolinska Institutet, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
3   Department of Cardiology, Karolinska University Hospital; Stockholm, Sweden
,
Angela Silveira
1   Atherosclerosis Research Unit, King GustafV Research Institute, Karolinska Institutet, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
› Author AffiliationsFinancial support: This study was supported by grants from the Swedish Medical Research Council (8691), the Swedish Heart-Lung Foundation, the Petrus and Augusta Hedlund Foundation, the King Gustaf V and Queen Victoria Foundation, the Foundation for Old Servants, the Professor Nanna Svartz Foundation, the Stockholm County Council and Karolinska Institutet.
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Publication History

Received 30 November 2005

Accepted after resubmission 24 January 2006

Publication Date:
29 November 2017 (online)

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Summary

An intricate interplay between the genes encoding fibrinogen gamma (FGG), alpha (FGA) and beta (FGB), coagulation factor XIII (F13A1) and interleukin6 (IL6) and environmental factors is likely to influence plasma fibrinogen concentration, fibrin clot structure and risk of myocardial infarction (MI). In the present study, the potential contribution of SNPs harboured in the fibrinogen, IL6 and F13A1 genes to these biochemical and clinical phenotypes was examined. A database and biobank based on 387 survivors ofa first MI and population-based controls were used. Sixty controls were selected according to FGG 9340T>C [rs1049636] genotype for studies on fibrin clot structure using the liquid permeation method. The multifactor dimensionality reduction method was used for interaction analyses. We here report that the FGA 2224G>A [rs2070011] SNP (9.2%), plasma fibrinogen concentration (13.1%) and age (8.1%) appeared as independent determinants of fibrin gel porosity. The FGA 2224G>A SNP modulated the relation between plasma fibrinogen concentration and fibrin clot porosity. The FGG-FGA*4 haplotype, composed of the minor FGG 9340C and FGA 2224A alleles, had similar effects, supporting its reported protective role in relation to MI. Significant epistasis on plasma fibrinogen concentration was detected between the FGA 2224G>A and F13A1 Val34Leu [rs5985] SNPs (p<0.001).The FGG 9340T>C and FGB 1038G>A [rs1800791] SNPs appeared to interact on MI risk, explaining the association of FGG-FGB haplotypes with MI in the absence of effects of individual SNPs. Thus, epistatic and pleiotropic effects of polymorphisms contribute to the variation in plasma fibrinogen concentration, fibrin clot structure and risk of MI.

Keywords

Epistasis - fibrinogen clot structure - myocardial infarction - plasma fibrinogen concentration - pleiotropy
 

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