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Dissecting the associations of endemic Pemphigus Foliaceus (Fogo Selvagem) with HLA-DRB1 alleles and genotypes

Genes & Immunity volume 4, pages 110–116 (2003)Cite this article

Abstract

Endemic pemphigus foliaceus (EPF) is a blistering skin disease characterized by autoantibodies against the desmosomal protein desmoglein 1. Genetic and environmental factors influence its pathogenesis. A total of 128 patients and 402 controls from an ethnically admixed Brazilian population were analyzed for associations by allele and genotype with HLA-DRB1. The alleles DRB1*0101, *0102, *0103, *0404, *0406, *0410, *1406 and *1601 are significantly more frequent among patients, while DRB1*0301, *0701, *0801, *1101, *1104 and *1402 are negatively associated to EPF. Results of association analysis with protein motifs composed of polymorphic amino-acid residues do not add much to comprehension of the molecular basis of the HLA-DRB1/EPF associations. Interactions between susceptible (SU), protective (PR) and neutral (NE) alleles clearly deviate from the codominant model. Protection is dominant, since the PR/NE and PR/PR genotypes are both equally (P=0.95) and strongly protective (odds ratio OR=0.07 and 0.05, respectively; P<10−6 for both). The SU/SU genotype confers a higher (P=0.012) risk than genotype SU/NE (OR=8.7 and 4.0; P<10−6 for both), an evidence of a semi-dominant effect of SU alleles relative to NE alleles. The OR for the SU/PR genotype (statistically close to 1) is consistent with semi-dominance between PR and SU alleles. Knowledge of these allelic interactions is relevant for understanding the mechanisms underlying autoimmune disease pathogenesis.

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Acknowledgements

We thank patients and control individuals for their collaboration and Márcia Machado de Oliveira Dalalio for providing some of the samples collected in Campo Grande. The physicians and the administration staff of the Hospital Adventista do Pênfigo are kindly acknowledged for their hospitality and information. This work was supported by the Brazilian National Research Council (CNPq), FUNPAR, PRPPG/UFPR and CAPES.

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Authors and Affiliations

  1. Laboratório de Genética Molecular Humana, Universidade Federal do Paraná, Curitiba, Brazil

    D P Pavoni, V M M S Roxo & M L Petzl-Erler

  2. Hospital Adventista do Pênfigo, Campo Grande, Brazil

    A Marquart Filho

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  1. D P Pavoni
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  2. V M M S Roxo
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  3. A Marquart Filho
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  4. M L Petzl-Erler
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Correspondence to M L Petzl-Erler.

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Pavoni, D., Roxo, V., Marquart Filho, A. et al. Dissecting the associations of endemic Pemphigus Foliaceus (Fogo Selvagem) with HLA-DRB1 alleles and genotypes. Genes Immun 4, 110–116 (2003). https://doi.org/10.1038/sj.gene.6363939

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