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Thrombomodulin gene polymorphisms in brain infarction and mortality after stroke

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Abstract

Background and purpose

Thrombomodulin is expressed at the surface of endothelial cells and controls thrombin generation and thrombin-induced platelets and vascular cell activation. Several thrombomodulin gene polymorphisms have been associated with coronary events and brain infarction. In a previous analysis from the Etude du Profil Génétique de l'Infarctus Cérébral (GENIC) study, we found that soluble thrombomodulin (sTM) concentration modulated the risk of and prognosis for brain infarction.

Methods

In 474 brain infarction cases and 483 controls from the GENIC study, we investigated the relationship between three thrombomodulin gene polymorphisms (–1748G/C, –1208/–1209delTT, +1418C/T) and sTM levels, brain infarction risk and 5-year mortality after stroke.

Results

The three polymorphisms were in linkage disequilibrium and defined three major haplotypes with no influence on sTM concentration (all P values > 0.16). Single locus and haplotype analyses found no significant association with brain infarction, even when the analysis was restricted to individuals without a vascular history. After 5 years of follow-up, we found no relationship with vascular or total mortality (all P values > 0.64).

Conclusion

Our results suggest that these three thrombomodulin gene polymorphisms do not contribute to sTM level variations and are not associated with risk of brain infarction and mortality after stroke.

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Authors and Affiliations

  1. INSERM U698 and Denis Diderot University – Paris VII, Dept. of Neurology and Stroke Center, Bichat University Hospital, Paris, France

    J.-M. Olivot MD, PhD, J. Labreuche BST &  P. Amarenco MD

  2. Dept. of Neurology, Delafontaine Hospital, Saint Denis, France

    T. De Broucker MD

  3. INSERM UMR S525 and Pierre and Marie Curie University –, Paris VI, Paris, France

    O. Poirier PhD & F. Cambien MD

  4. INSERM U428 and René Descartes University – Paris V, Dept. of Haematology and Haemostasis, Georges Pompidou Hospital, Paris, France

    J.-M. Olivot MD, PhD & M. Aiach PhD

  5. Coordinating Centre for the GENIC study, Dept. of Neurology and Stroke Center, Bichat Hospital, 46, rue Henri Huchard, 75018, Paris, France

    P. Amarenco MD

Authors
  1. J.-M. Olivot MD, PhD
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  2. J. Labreuche BST
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  3. T. De Broucker MD
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  4. O. Poirier PhD
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  5. F. Cambien MD
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  6. M. Aiach PhD
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  7. P. Amarenco MD
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Consortia

for the GENIC Investigators*

Corresponding author

Correspondence to P. Amarenco MD.

Additional information

*A list of the GENIC Investigators is available at http://genic.medecine.univ-paris7.fr.

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Olivot, JM., Labreuche, J., De Broucker, T. et al. Thrombomodulin gene polymorphisms in brain infarction and mortality after stroke. J Neurol 255, 514–519 (2008). https://doi.org/10.1007/s00415-008-0725-x

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  • DOI: https://doi.org/10.1007/s00415-008-0725-x

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