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Thromb Haemost 2008; 100(02): 308-313
DOI: 10.1160/TH07-11-0704
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Variation in fibrinogen FGG and FGA genes and risk of stroke

The Rotterdam Study
Elim Y. L. Cheung   *
1   Department of Hematology
,
Michiel J. Bos   *
2   Department of Epidemiology & Biostatistics
3   Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands
,
Frank W. G. Leebeek
1   Department of Hematology
,
Peter J. Koudstaal
3   Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands
,
Albert Hofman
2   Department of Epidemiology & Biostatistics
,
Moniek P. M. de Maat
1   Department of Hematology
,
Monique M. B. Breteler
2   Department of Epidemiology & Biostatistics
› Author AffiliationsFinancial support: This study was supported by a grant from the Dutch program for Tissue Engineering. The Rotterdam Study is supported by Erasmus MC (Erasmus Medical Center Rotterdam), the Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMW), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, and the Ministry of Health, Welfare and Sports. This study was supported by the Netherlands Organization for Scientific Research (NWO) grants 904–61–093 and 918–46–615.
Further Information

Publication History

Received 28 November 2007

Accepted after major revision 29 May 2008

Publication Date:
22 November 2017 (online)

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Summary

Haplotypes of the fibrinogen gamma and alpha (FGG and FGA) genes are associated with the structure of the fibrin network and may therefore influence the risk of stroke. We investigated the relationship between common variation in these genes with ischemic and haemorrhagic stroke. The study was based on 6,275 participants of the prospective population-based Rotterdam Study who at baseline (1990 – 1993) were aged 55 years or over, free from stroke, and had successful assessment of at least one FGG or FGA single nucleotide polymorphisms (SNP). Common haplotypes were estimated using seven tagging SNPs across a 30 kb region containing the FGG and FGA genes. Follow-up for incident stroke was complete until January 1,2005. Associations between constructed haplotypes and risk of stroke were estimated with an age- and sex-adjusted logistic regression model. We observed 668 strokes, of which 393 were ischemic and 62 haemorrhagic, during a median follow-up time of 10.1 years. FGG+FGA haplotype 3 (H3) was associated with an increased risk of ischemic stroke (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.09–1.69) and the risk estimate for hemorrhagic stroke was 0.71 (95% CI 0.46–1.09) compared to the most frequent H1. The FGG and FGA genes were not associated with stroke or its subtypes when analyzed separately. In conclusion, risk of ischemic stroke was higher in FGG+FGA H3 than in H1. The results suggested that an opposite association may exist for haemorrhagic stroke.

Keywords

Stroke - fibrinogen - haplotype

* These authors contributed equally to this work.


 

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