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Thromb Haemost 2008; 99(02): 388-395
DOI: 10.1160/TH07-08-0523
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Associations between common fibrinogen gene polymorphisms and cardiovascular disease in older adults

The Cardiovascular Health Study
Cara L. Carty
1   Department of Epidemiology, University of Washington, Seattle, Washington, USA
,
Mary Cushman
2   Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
,
Daniel Jones
2   Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
,
Leslie A. Lange
3   Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA
,
Lucia A. Hindorff
1   Department of Epidemiology, University of Washington, Seattle, Washington, USA
,
Kenneth Rice
4   Department of Biostatistics, University of Washington, Seattle, Washington, USA
,
Nancy S. Jenny
1   Department of Epidemiology, University of Washington, Seattle, Washington, USA
,
J. Peter Durda
2   Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
,
Jeremy Walston
2   Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
,
Christopher S. Carlson
5   Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland, USA
,
Debbie Nickerson
6   Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
,
Russell P. Tracy
7   Department of Genome Sciences, University of Washington, Seattle, Washington, USA
,
Alex P. Reiner
2   Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
› Author Affiliations
Further Information

Publication History

Received: 27 August 2007

Accepted after major revision: 23 January 2007

Publication Date:
24 November 2017 (online)

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Summary

Elevated plasma fibrinogen is a risk factor for cardiovascular disease (CVD), but associations between fibrinogen single nucleotide polymorphisms (SNPs) and disease risk are inconsistent. We investigated whether common (≥ 5% minor allele frequency) variation in the fibrinogen genes (FGA, FGB, FGG) is associated with fibrinogen concentration, carotid artery intima-medial thickness (IMT) and risk of incident myocardial infarction (MI), ischemic stroke and CVD mortality in European-(EA) and African-descent (AA) adults (≥ 65 years) from the Cardiovascular Health Study. TagSNPs were genotyped in 3,969 EA and 719 AA free of MI or stroke at baseline. Race-specific models included multiple testing correction and adjustment for sex, age and site. Among EA, minor alleles of FGA3807,FGB1437 and FGG902 were associated with higher fibrinogen levels; whereas FGA251, FGA2224, FGA6534 and FGG10034 were associated with lower levels, p<0.004 for each. Strongest associations were seen for FGB1437;each additional copy of the minor allele was associated with 13 mg/dl (95%CI: 9–16) higher fibrinogen level. Similar trends in AA were not significant. Fibrinogen haplotypes were not significantly associated with internal or common carotid IMT. No associations with MI or CVD mortality were seen in EA, though FGB1038 and FGG902 were significantly associated with increased and decreased risk of stroke in men, respectively, as were related haplotypes. FGB1038 was also associated with CVD mortality in AA, HR=1.9 (95%CI: 1.3–2.7). In conclusion, while fibrinogen genetic variation was strongly associated with fibrinogen levels, there was less evidence of association with the more complex outcomes of IMT and CVD events.

Keywords

Fibrinogen - epidemiological studies - atherosclerosis - single nucleotide polymorphisms

 

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