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The TLR4 +896 polymorphism is not associated with lipopolysaccharide hypo-responsiveness in leukocytes

Genes & Immunity volume 6, pages 37–43 (2005)Cite this article

Abstract

Toll-like receptor 4 (TLR-4) is required for detection of Gram negative bacterial infections by binding lipopolysaccharide (LPS) and for the initiation of inflammatory signaling. Recent studies have demonstrated that a nonsynonymous single-nucleotide polymorphism (Asp299Gly, A+896G) is associated with decreased endotoxin responsiveness and poor outcomes from sepsis. We show that human carriers of this polymorphism show no deficit in LPS induced peripheral blood mononuclear cell (PBMC) mitogen-activated protein kinase (MAPK) activity, no reduction in sensitivity to endotoxin, and variable differences in whole-blood inflammatory cytokine production. These results indicate that this mutation is not a primary determinant of human endotoxin sensitivity.

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Authors and Affiliations

  1. Department of Surgery, University of Washington and Harborview Medical Center, USA

    S D Imahara, S Jelacic, C E Junker & G E O'Keefe

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  1. S D Imahara
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  2. S Jelacic
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  3. C E Junker
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Correspondence to S D Imahara.

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Grant support: T32 GM 07037.

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Imahara, S., Jelacic, S., Junker, C. et al. The TLR4 +896 polymorphism is not associated with lipopolysaccharide hypo-responsiveness in leukocytes. Genes Immun 6, 37–43 (2005). https://doi.org/10.1038/sj.gene.6364147

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