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Haplotypes of the fibrinogen gene and cerebral small vessel disease. The Rotterdam scan study
  1. Marieke van Oijen
  1. Erasmus Medical Center, Netherlands
    1. Elim Y.L. Cheung
    1. Erasmus Medical Center, Netherlands
      1. Claire E.M. Geluk
      1. Erasmus Medical Center, Netherlands
        1. Albert Hofman
        1. Erasmus Medical Center, Netherlands
          1. Peter J. Koudstaal
          1. Erasmus Medical Center, Netherlands
            1. Monique M.B. Breteler (m.breteler{at}erasmusmc.nl)
            1. Erasmus Medical Center, Netherlands
              1. Moniek P. de Maat
              1. Erasmus Medical Center, Netherlands

                Abstract

                Obkective: Fibrinogen levels and fibrinogen clot structure have been implicated in pathogenesis of vascular disease. We examined fibrinogen levels and variation in fibrinogen genes (fibrinogen γ (FGG), α (FGA) and β (FGB)), associated with fibrin clot structure and fibrinogen levels, in relation to cerebral small vessel disease (SVD).

                Methods and Results This study was performed in the Rotterdam Scan Study, a population-based study among 1077 elderly with cerebral magnetic resonance imaging. Plasma fibrinogen levels and haplotypes were determined. We examined the association of fibrinogen levels and haplotypes with silent brain infarcts and white matter lesions by means of logistic regression models. We constructed seven haplotypes (frequency >0.01) that describe the total common variation in the FGG and FGA genes. Haplotype 2 (G-A-T-A-G-T-G) was associated with presence of silent brain infarcts when compared to the most frequent haplotype (G-G-T-G-G-T-A) (odds ratio (OR) 1.41, 95% CI 1.03-1.94). Haplotype 3 (G-G-C-G-A-T-A) was associated with periventricular white matter lesions in the highest tertile of the distribution (OR 1.40, 95% CI 1.01-1.92). No association was found between plasma fibrinogen levels and SVD.

                Conclusions Our study provides evidence for an association of common variation in the FGG and FGA genes with cerebral SVD. Possibly, structure of the fibrin clot rather than plasma fibrinogen levels plays a role in the pathogenesis of cerebral SVD.

                • fibrinogen
                • haplotypes
                • silent brain infarct
                • white matter lesion

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