title: Both qualitative and quantitative genetic variation of MHC class II molecules may influence susceptibility to autoimmune diseases: the case of endemic pemphigus foliaceus.
abstract: The MHC class II transactivator (CIITA) is a key regulator in expression of the HLA class II genes. It is well known that HLA-DRB1 genotypes have a strong influence on the risk of multifactorial autoimmune diseases, but the effect of CIITA genotypes remains controversial. We tested in a case-control study whether CIITA polymorphisms influence the risk of developing endemic pemphigus foliaceus (EPF) and whether CIITA and HLA-DRB1 interact as regards susceptibility to the disease. The rs4774 SNP is not associated to EPF, while rs3087456 in the CIITA gene promoter is associated with susceptibility [odds ratio (OR) = 2.6, p < 0.001 and OR = 2.0 p = 0.003 for genotypes G/G and G/A, respectively]. We suggest that the associations result from the effect of genetically controlled levels of CIITA on expression of the susceptible and protective HLA class II molecules. Remarkably, the interaction between CIITA and HLA-DRB1 genotypes is strong and additive. The OR for individuals having two susceptible HLA-DRB1 alleles is 14.1 in presence of the susceptible CIITA G/G or G/A genotypes and much lower (2.2) in presence of the protective CIITA A/A genotype. We conclude that quantitative as well as qualitative variation of HLA class II molecules have an effect on the risk of an individual developing EPF.
authors.affiliation: Laboratório de Genética Molecular Humana, Departamento de Genética, Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Bruno Zagonel
authors.initials: BZ
authors.lastname: Piovezan
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Petzl-Erler
mesh_terms: D044383:Black People; D001938:Brazil; D016022:Case-Control Studies; D019353:Endemic Diseases; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D010392:Pemphigus / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D015534:Trans-Activators / Q000235:genetics*; D044465:White People
chemical_list: D059811:HLA-DRB1 Chains; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators
keywords: CI; CIITA; EPF; MHC; NE; OR; P; PR; SNP; SU; Treg; class II, major histocompatibility complex, transactivator; confidence interval; endemic pemphigus foliaceus; major histocompatibility complex; neutral allele; odds ratio; probability; protective allele; regulatory T cells; single nucleotide polymorphism; susceptibility allele