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Epistasis between DSG1 and HLA class II genes in pemphigus foliaceus

Genes & Immunity volume 3, pages 205–210 (2002)Cite this article

Abstract

Pemphigus foliaceus (PF) is a rare and severe cutaneous autoimmune disease caused by autoantibodies directed against desmoglein 1 (DSG1), a desmosomal adhesion glycoprotein. We previously showed that the DSG1 gene is polymorphic and that a coding synonymous T/C single nucleotide polymorphism at position 809 is associated with PF. To determine whether the disease occurred as a consequence of complex genetic interactions, we simultaneously examined the contribution of major histocompatibility complex (MHC) class II and DSG1 polymorphisms to PF susceptibility. Our analysis performed in 31 PF patients and 84 healthy controls first confirmed the previously reported common DRB1*04 and DRB1*14 genetic background in PF and individualized DRB1*0102, DRB1*0402 and DRB1*0406, and DRB1*1404 as susceptibility MHC class II alleles in French Caucasian PF patients. It also showed that the C/C(809) genotype was associated with PF. Combined analysis of HLA class II and DSG1 polymorphisms with several distinct statistical methods including logistic regression, showed that the DRB1*04 allele and the C/C(809) genotype interact to confer a higher susceptibility to PF. These data demonstrate the role of epistasis between individual genes in PF susceptibility and illustrate the genetic complexity of organ-specific autoimmune diseases.

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Acknowledgements

We are indebted to Dr Dominique Campion for helpful discussion and reading the manuscript, and Janet Jacobson for editing the manuscript.

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Authors and Affiliations

  1. INSERM U519, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides (IFR23), Faculté de Médecine et Hôpital Charles Nicolle, Rouen, France

    P Martel, D Gilbert, L Drouot, P Joly & F Tron

  2. Laboratoire d’Immunologie et d’Histocompatibilité and INSERM U396, Hôpital Saint-Louis, Paris, France

    M Busson, P Loiseau, V Lepage & D Charron

  3. Service de Dermatologie, Hôpital Claude Huriez, Lille, France

    E Delaporte

  4. Service de Dermatologie, Hôpital Saint-Louis, Paris, France

    C Prost

  5. Clinique Dermatologique, Hôpital Charles Nicolle, Rouen, France

    P Joly

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  1. P Martel
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  2. D Gilbert
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  3. M Busson
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  10. D Charron
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Correspondence to P Martel.

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This work has been supported by grants from the Institut National de la Santé et de la Recherche Médicale.

Authors disclose any financial interest that may constitute a conflict of interest.

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Martel, P., Gilbert, D., Busson, M. et al. Epistasis between DSG1 and HLA class II genes in pemphigus foliaceus. Genes Immun 3, 205–210 (2002). https://doi.org/10.1038/sj.gene.6363839

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