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Molecular Medicine

, Volume 14, Issue 5–6, pp 346–352 | Cite as

Functional Consequences of Toll-like Receptor 4 Polymorphisms

  • Bart Ferwerda
  • Matthew B. B. McCall
  • Karlijn Verheijen
  • Bart-Jan Kullberg
  • André J. A. M. van der Ven
  • Jos W. M. Van der Meer
  • Mihai G. Netea
Review Article

Abstract

Toll-like receptor 4 (TLR4) is an important pathogen recognition receptor that recognizes mainly lipopolysaccharide (LPS) of Gram-negative bacteria, but also structures from fungal and mycobacterial pathogens, as well as endogenous ligands. Two nonsynonymous polymorphisms of TLR4, Asp299Gly and Thr399lle, have been suggested to alter the function of the receptor. Some, but not all, studies have proposed that these polymorphisms lead to reduced cytokine response and increased susceptibility to Gram-negative infections. In this review, we compare studies that assessed the effect of the Asp299Gly and Thr399lle polymorphisms on susceptibility to Gram-negative infections and examine the phenotypic consequences of these polymorphisms. In addition, we review the geographical distribution of TLR4 polymorphisms and present a model for evolutionary pressures on the TLR4 genetic make-up.

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Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Bart Ferwerda
    • 1
    • 2
  • Matthew B. B. McCall
    • 1
    • 3
  • Karlijn Verheijen
    • 1
    • 2
  • Bart-Jan Kullberg
    • 1
    • 2
  • André J. A. M. van der Ven
    • 1
    • 2
  • Jos W. M. Van der Meer
    • 1
    • 2
  • Mihai G. Netea
    • 1
    • 2
  1. 1.Department of Internal MedicineRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  2. 2.Nijmegen University Center for Infectious DiseasesNijmegenThe Netherlands
  3. 3.Department of ParasitologyNijmegenThe Netherlands

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