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Initial description of the human NLRP3 promoter

Genes & Immunity volume 9, pages 721–726 (2008)Cite this article

Abstract

Mutations in NLRP3 (CIAS1) are identified in a continuum of related inflammatory disorders, known as cryopyrinopathies since NLRP3 codes for the protein cryopyrin. Approximately 40% of patients with classic presentation lack mutations in the coding region of NLRP3 suggesting heterogeneity or epigenetic factors. Cryopyrin is a key regulator of proinflammatory cytokine release. Therefore, variations in the NLRP3 promoter sequence may have effects on disease state in patients with cryopyrinopathies and other inflammatory diseases. In this report, we confirmed three 5′-untranslated region splice forms with two separate transcriptional start sites, and identified potential promoter regions and six new DNA promoter variants. One variant is unique to a mutation negative cryopyrinopathy patient and increases in vitro gene expression. Additional studies can now be performed to further characterize the NLRP3 promoter and sequence variants, which will lead to better understanding of the regulation of NLRP3 expression and its role in disease.

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Authors and Affiliations

  1. Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA

    J P Anderson

  2. School of Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA

    J P Anderson & A Misaghi

  3. Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA

    J L Mueller, S Anderson, M Sivagnanam & H M Hoffman

  4. Ludwig Institute of Cancer Research, University of California San Diego School of Medicine, La Jolla, CA, USA

    J L Mueller, R D Kolodner & H M Hoffman

  5. Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA

    R D Kolodner

  6. Department of Cellular and Molecular Medicine and Cancer Center, University of California San Diego School of Medicine, La Jolla, CA, USA

    R D Kolodner

  7. Division of Rheumatology, Allergy, and Immunology, University of California San Diego School of Medicine, La Jolla, CA, USA

    H M Hoffman

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  1. J P Anderson
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  2. J L Mueller
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  3. A Misaghi
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  4. S Anderson
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  5. M Sivagnanam
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  6. R D Kolodner
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  7. H M Hoffman
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Corresponding author

Correspondence to H M Hoffman.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Anderson, J., Mueller, J., Misaghi, A. et al. Initial description of the human NLRP3 promoter. Genes Immun 9, 721–726 (2008). https://doi.org/10.1038/gene.2008.66

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  • DOI: https://doi.org/10.1038/gene.2008.66

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