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Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo

Open access
Jin, Ying, Birlea, Stanca A., Fain, Pamela R., Gowan, Katherine, Riccardi, Sheri L., Holland, Paulene J., Mailloux, Christina M., Sufit, Alexandra J.D., Hutton, Saunie M., Amadi-Myers, Anita, Bennett, Dorothy C., Wallace, Margaret R., McCormack, Wayne T., Kemp, E. Helen, Gawkrodger, David J., Weetman, Anthony P., Picardo, Mauro, Leone, Giovanni, Taïeb, Alain, Jouary, Thomas, Ezzedine, Khaled, van Geel, Nanny, Lambert, Jo, Overbeck, Andreas, Spritz, Richard A.·2010·New England Journal of Medicine

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=9.05x10(-23)) and class II molecules (P=4.50x10(-34)), PTPN22 (P=1.31x10(-7)), LPP (P=1.01x10(-11)), IL2RA (P=2.78x10(-9)), UBASH3A (P=1.26x10(-9)), and C1QTNF6 (P=2.21x10(-16)). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07x10(-15)) and GZMB (P=3.44x10(-8)), and in a locus containing TYR (P=1.60x10(-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.

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Metadata

Authors
Jin, Y., Birlea, S. A., Fain, P. R., Gowan, K., Riccardi, S. L., Holland, P. J., Mailloux, C. M., Sufit, A. J. D., Hutton, S. M., Amadi-Myers, A., Bennett, D. C., Wallace, M. R., McCormack, W. T., Kemp, E. H., Gawkrodger, D. J., Weetman, A. P., Picardo, M., Leone, G., Taïeb, A., Jouary, T., Ezzedine, K., van Geel, N., Lambert, J., Overbeck, A., & Spritz, R. A.
Venue
New England Journal of Medicine
Published
2010-05-06
Volume
362
Issue
18
Pages
1686-1697
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W2141665982
Cited by
415
References
6
FWCI
15.70
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo. https://app.cochat.ai/papers/10.1056/nejmoa0908547
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Jin, Y., Birlea, S. A., Fain, P. R., Gowan, K., Riccardi, S. L., Holland, P. J., Mailloux, C. M., Sufit, A. J. D., Hutton, S. M., Amadi-Myers, A., Bennett, D. C., Wallace, M. R., McCormack, W. T., Kemp, E. H., Gawkrodger, D. J., Weetman, A. P., Picardo, M., Leone, G., Taïeb, A., . . . Spritz, R. A. (2010). Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo. New England Journal of Medicine. https://doi.org/10.1056/nejmoa0908547

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.