title: Pemphigus foliaceus and desmoglein 1 gene polymorphism: is there any relationship?
abstract: Transmembrane proteins of the cadherin superfamily, the desmogleins and desmocollins, mediate intercellular adhesion in desmosomes. Autoantibodies to desmoglein 1 (dsg1) are a hallmark of pemphigus foliaceus (PF), a disease characterized by skin blistering resulting from keratinocyte cell detachment. The etiology and pathogenesis of this disease remain poorly understood; however, genetic susceptibility is clearly involved. The aim of this study was to verify if genetic variants of dsg1 influence susceptibility/resistance to endemic PF (fogo selvagem). Two single nucleotide polymorphisms (SNPs) were analyzed: 809 (C,T), a synonymous variation, and 1660 (A,C), a tyrosine<-->serine variation in the fifth extracellular domain. Allelic, haplotypic and genotypic frequencies did not differ significantly between the patient (n=134) and the control (n=227) population samples. Moreover, there is no evidence of interaction between the DSG1 and the HLA-DRB1 and IL6 genes, whose alleles had been found associated with differential susceptibility to PF. The results of this study agree with the described and predicted B- and T-cell epitopes of the dsg1 molecule, which seemingly are not affected by the allelic variation. We conclude that genetic diversity of the autoantigen dsg1 is not a major factor for PF pathogenesis in the Brazilian population.
authors.affiliation: Human Molecular Genetics Laboratory, Department of Genetics, Federal University of Paraná, Caixa Postal 19071, 81531-990 Curitiba, Brazil. perler@ufpr.br
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Petzl-Erler
authors.forename: Danielle
authors.initials: D
authors.lastname: Malheiros
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D001938:Brazil; D051183:Desmoglein 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D010392:Pemphigus / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic
chemical_list: D051183:Desmoglein 1