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High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR

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Abstract

The recently described family of Toll-like receptors (TLRs) plays a major role in innate immunity by mediating inflammatory reactions against a wide array of pathogens. TLR-2 is reported to interact with various bacterial partial structures including lipoproteins, peptidoglycan, and lipoteichoic acid. Two polymorphisms of the TLR-2 gene have recently been described: Arg753Gln, correlated with the incidence of sepsis in a white population, and Arg677Trp, correlated with the incidence of lepromatous leprosy in an Asian population. Both polymorphisms, when inserted into expression vectors encoding for human TLR-2, reduced stimulation of Chinese hamster ovary cells by synthetic lipopeptides. We furthermore developed a rapid and inexpensive method for the detection of both single nucleotide polymorphisms based on restriction fragment length polymorphism. While no individuals carrying the Arg677Trp SNP were identified in a large group of whites, 9.4% of the study population were found to be heterozygous for the Arg753Gln polymorphism. This ratio is significantly higher than previously reported, and therefore detection of this polymorphism among patients may yield important information for the assessment of risk profiles regarding susceptibility to bacterial infections.

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Abbreviations

CHO :

Chinese hamster ovary

ELAM :

Endothelial cell/leukocyte adhesion molecule nuclear transcription factor κB luciferase reporter plasmid

PCR :

Polymerase chain reaction

RFLP :

Restriction fragment length polymorphism

SNP :

Single nucleotide polymorphism

TLR :

Toll-like receptor

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Acknowledgements

This work was supported in part by grants from the German Bundesministerium für Bildung und Forschung to R.R.S. (CAPNetz) and Deutsche Forschungsgemeinschaft to R.R.S. and N.W.J.S. (Innate Immunity).

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Authors and Affiliations

  1. Institut für Mikrobiologie und Hygiene, Universitätsklinikum Charité, Medizinische Fakultät, Humboldt-Universität zu Berlin, Dorotheenstrasse 96, 10098, Berlin, Germany

    Nicolas W. J. Schröder, Lutz Hamann, Ulf B. Göbel & Ralf R. Schumann

  2. Department of Biochemical Pharmacology, University of Constance, Box M 665, 78457, Constance, Germany

    Corinna Hermann & Thomas Hartung

Authors
  1. Nicolas W. J. Schröder
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  2. Corinna Hermann
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  3. Lutz Hamann
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  4. Ulf B. Göbel
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  5. Thomas Hartung
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  6. Ralf R. Schumann
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Correspondence to Ralf R. Schumann.

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Schröder, N.W.J., Hermann, C., Hamann, L. et al. High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR. J Mol Med 81, 368–372 (2003). https://doi.org/10.1007/s00109-003-0443-x

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  • DOI: https://doi.org/10.1007/s00109-003-0443-x

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