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A functional polymorphism of the vasoactive intestinal peptide receptor 1 gene correlates with the presence of HLA-B *2705 in Sardinia

Genes & Immunity volume 9, pages 659–667 (2008)Cite this article

Abstract

The association of HLA-B27 with ankylosing spondylitis (AS) is the strongest among all inflammatory diseases. However, the exact role of these molecules in disease pathogenesis is still unknown. The existence of HLA-B27 variants rarely found in patients introduces a further level of complexity. It is now accepted that other genes of minor impact contribute to modify disease susceptibility and these genes might be diverse in different populations depending on the genetic background. We report here a study performed in Sardinia, an outlier population in which two major HLA-B27 subtypes are present, B *2705 strongly associated with AS and B *2709 which is not, and show the co-occurrence of the B *2705 allele with a single nucleotide polymorphism (SNP) mapping at 3′-UTR of the receptor 1 (VIPR1) for the vasoactive intestinal peptide (VIP), a neuropeptide with anti-inflammatory properties. This same SNP is associated with a different kinetics of down-modulation of the VIPR1 mRNA in monocytes after exposure to lipopolysaccharide (P=0.004). This particular setting, HLA-B *2705 and a functional polymorphism in VIPR1 gene, might be due to a founder effect or might be the result of a selective pressure. Irrespectively, the consequent downregulation of this receptor in the presence of a ‘danger’ signal might influence susceptibility to AS.

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Acknowledgements

We thank the patients for their cooperation and Federica Lucantoni for technical assistance. A special thank to Dr Kathleen Freson for providing the anti-VIPR1 polyclonal antibody. This work has been partially supported by Fondazione Cenci-Bolognetti, ‘Sapienza’ University of Rome.

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Authors and Affiliations

  1. Department of Cell Biology and Development, ‘Sapienza’ University of Rome, Roma, Italy

    F Paladini, E Cocco, M T Fiorillo & R Sorrentino

  2. Department of Medical Sciences, University of Cagliari, Cagliari, Italy

    A Cauli, A Vacca & A Mathieu

  3. Cell Biology Institute, CNR, Monterotondo Scalo, Roma, Italy

    I Cascino & F Belfiore

  4. Istituto Pasteur-Fondazione Cenci Bolognetti, ‘Sapienza’ University of Rome, Roma, Italy

    R Sorrentino

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  1. F Paladini
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Correspondence to R Sorrentino.

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Paladini, F., Cocco, E., Cauli, A. et al. A functional polymorphism of the vasoactive intestinal peptide receptor 1 gene correlates with the presence of HLA-B *2705 in Sardinia. Genes Immun 9, 659–667 (2008). https://doi.org/10.1038/gene.2008.60

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