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.
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Acknowledgements
We are grateful to the many vitiligo patients and family members who provided blood samples for this research. We thank Margaret R Wallace, Sally A Litherland and Susan P McGorray for helpful discussions and thoughtful critique of the manuscript. This work was supported by grants from the National Vitiligo Foundation and by Clinical Research Center Grant RR00082. CBC was supported by a training grant from the National Institutes of Health (T32 AR 07603), and by the UF Center for Immunology & Transplantation.
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Casp, C., She, JX. & McCormack, W. Genes of the LMP/TAP cluster are associated with the human autoimmune disease vitiligo. Genes Immun 4, 492–499 (2003). https://doi.org/10.1038/sj.gene.6364016
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DOI: https://doi.org/10.1038/sj.gene.6364016
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