Jin, Y., Birlea, S.A., Fain, P.R. et al. (22 more authors) (2010) Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo. New England Journal of Medicine, 362 (18). pp. 1686-1697. ISSN 0028-4793
Abstract
BACKGROUND Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases.
METHODS To identify generalized vitiligo susceptibility loci, we conducted a genomewide association study. We genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1514 patients with generalized vitiligo who were of European-derived white (CEU) ancestry and compared the genotypes with publicly available control genotypes from 2813 CEU persons. We then tested 50 SNPs in two replication sets, one comprising 677 independent CEU patients and 1106 CEU controls and the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families.
RESULTS We detected significant associations between generalized vitiligo and SNPs at several loci previously associated with other autoimmune diseases. These included genes encoding major-histocompatibility-complex class I molecules (P=9.05×10−23) and class II molecules (P=4.50×10−34), PTPN22 (P=1.31×10−7), LPP (P=1.01×10−11), IL2RA (P=2.78×10−9), UBASH3A (P=1.26×10−9), and C1QTNF6 (P=2.21×10−16). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07×10−15) and GZMB (P=3.44×10−8), and in a locus containing TYR (P=1.60×10−18), encoding tyrosinase.
CONCLUSIONS We observed associations between generalized vitiligo and markers implicating multiple genes, some associated with other autoimmune diseases and one (TYR) that may mediate target-cell specificity and indicate a mutually exclusive relationship between susceptibility to vitiligo and susceptibility to melanoma.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2010 Massachusetts Medical Society. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | Autoimmune Diseases; Genetic Markers; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Major Histocompatibility Complex; Melanoma; Monophenol Monooxygenase; Polymorphism, Single Nucleotide; Vitiligo |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 18 Nov 2019 14:16 |
Last Modified: | 18 Nov 2019 14:16 |
Status: | Published |
Publisher: | Massachusetts Medical Society |
Refereed: | Yes |
Identification Number: | 10.1056/NEJMoa0908547 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:152630 |