title: Dissecting the associations of endemic pemphigus foliaceus (Fogo Selvagem) with HLA-DRB1 alleles and genotypes.
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.
authors.affiliation: Laboratório de Genética Molecular Humana, Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: D P
authors.initials: DP
authors.lastname: Pavoni
authors.forename: V M M S
authors.initials: VM
authors.lastname: Roxo
authors.forename: A
authors.initials: A
authors.lastname: Marquart Filho
authors.forename: M L
authors.initials: ML
authors.lastname: Petzl-Erler
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D019353:Endemic Diseases; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D010392:Pemphigus / Q000453:epidemiology / Q000235:genetics*
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen