title: Genes of the LMP/TAP cluster are associated with the human autoimmune disease vitiligo.
abstract: Genes within the class II region of the major histocompatibility complex (MHC), including genes involved in antigen processing and presentation, have been reported to be associated with several autoimmune diseases. We report here that the LMP/TAP gene region is significantly associated with vitiligo, a disorder in which biochemical defects and/or autoimmune destruction cause melanocyte loss and resulting skin depigmentation. Case/control analyses revealed genetic association of vitiligo in Caucasian patients with an early age of onset with the transporter associated with antigen processing-1 (TAP1) gene. A family-based association method revealed biased transmission of specific alleles from heterozygous parents to affected offspring for the TAP1 gene, as well as for the closely linked LMP2 and LMP7 genes encoding subunits of the immunoproteasome. No association with vitiligo was found for the MECL1 gene, which encodes a third immunoproteasome subunit and is unlinked to the MHC class II region. These results suggest a possible role for the MHC class I antigen processing and/or presentation pathway in the antimelanocyte autoimmune response involved in vitiligo pathogenesis.
authors.affiliation: Department of Pathology, Immunology & Laboratory Medicine, Centers for Mammalian Genetics and Immunology & Transplantation, University of Florida College of Medicine, Gainesville, FL 32610-0275, USA. mccormac@pathology.ufl.edu
authors.forename: C B
authors.initials: CB
authors.lastname: Casp
authors.forename: J-X
authors.initials: JX
authors.lastname: She
authors.forename: W T
authors.initials: WT
authors.lastname: McCormack
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D017951:Antigen Presentation / Q000235:genetics; D002170:Canada; D016022:Case-Control Studies; D003546:Cysteine Endopeptidases / Q000235:genetics*; D005802:Genes, MHC Class II / Q000276:immunology*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D009097:Multienzyme Complexes; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex; D014481:United States; D014820:Vitiligo / Q000235:genetics*; D044465:White People
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D009097:Multienzyme Complexes; C073119:TAP1 protein, human; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex