Risk of Generalized Vitiligo is Associated with the Common 55R-94A-247H Variant Haplotype of GZMB (Encoding Granzyme B)

Risk of Generalized Vitiligo is Associated with the Common 55R-94A-247H Variant Haplotype of GZMB (Encoding Granzyme B)

Generalized vitiligo (GV) is characterized by autoimmune destruction of melanocytes by skin-homing cytotoxic T-cells (CTLs) that target melanocyte autoantigens. Two recent genomewide association studies (GWAS) of GV in European-derived whites (EUR) have demonstrated genetic association with GZMB, en...

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Main Authors: Ferrara, Tracey M., Jin, Ying, Gowan, Katherine, Fain, Pamela R., Spritz, Richard A.
Format: Online
Language:English
Published: 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634907/
id pubmed-3634907
recordtype oai_dc
spelling pubmed-36349072013-12-01 Risk of Generalized Vitiligo is Associated with the Common 55R-94A-247H Variant Haplotype of GZMB (Encoding Granzyme B) Ferrara, Tracey M. Jin, Ying Gowan, Katherine Fain, Pamela R. Spritz, Richard A. Article Generalized vitiligo (GV) is characterized by autoimmune destruction of melanocytes by skin-homing cytotoxic T-cells (CTLs) that target melanocyte autoantigens. Two recent genomewide association studies (GWAS) of GV in European-derived whites (EUR) have demonstrated genetic association with GZMB, encoding granzyme B, a marker of activated CTLs that mediates target-cell apoptosis, as well as autoantigen activation and consequent initiation and propagation of autoimmunity. Here, we describe detailed genetic analyses of the GZMB region of chromosome 14q12 to identify genetic variation potentially causal for GV, implicating two non-synonymous SNPs in strong linkage disequilibrium that comprise part of a common multi-variant high-risk haplotype, rs8192917-C— rs11539752-C (55R-94A). To identify possible uncommon deleterious variants that might “hitchhike” on the high-risk haplotype, we then carried out “next-generation” DNA re-sequencing of GZMB in 114 EUR GV patients. Overall, our findings support a direct causal role for the GZMB rs8192917-C—rs11539752-C haplotype (55R-94A) in the pathogenesis of GV. 2013-01-15 2013-06 /pmc/articles/PMC3634907/ /pubmed/23321921 http://dx.doi.org/10.1038/jid.2013.5 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ferrara, Tracey M.
Jin, Ying
Gowan, Katherine
Fain, Pamela R.
Spritz, Richard A.
spellingShingle Ferrara, Tracey M.
Jin, Ying
Gowan, Katherine
Fain, Pamela R.
Spritz, Richard A.
Risk of Generalized Vitiligo is Associated with the Common 55R-94A-247H Variant Haplotype of GZMB (Encoding Granzyme B)
author_facet Ferrara, Tracey M.
Jin, Ying
Gowan, Katherine
Fain, Pamela R.
Spritz, Richard A.
author_sort Ferrara, Tracey M.
title Risk of Generalized Vitiligo is Associated with the Common 55R-94A-247H Variant Haplotype of GZMB (Encoding Granzyme B)
title_short Risk of Generalized Vitiligo is Associated with the Common 55R-94A-247H Variant Haplotype of GZMB (Encoding Granzyme B)
title_full Risk of Generalized Vitiligo is Associated with the Common 55R-94A-247H Variant Haplotype of GZMB (Encoding Granzyme B)
title_fullStr Risk of Generalized Vitiligo is Associated with the Common 55R-94A-247H Variant Haplotype of GZMB (Encoding Granzyme B)
title_full_unstemmed Risk of Generalized Vitiligo is Associated with the Common 55R-94A-247H Variant Haplotype of GZMB (Encoding Granzyme B)
title_sort risk of generalized vitiligo is associated with the common 55r-94a-247h variant haplotype of gzmb (encoding granzyme b)
description Generalized vitiligo (GV) is characterized by autoimmune destruction of melanocytes by skin-homing cytotoxic T-cells (CTLs) that target melanocyte autoantigens. Two recent genomewide association studies (GWAS) of GV in European-derived whites (EUR) have demonstrated genetic association with GZMB, encoding granzyme B, a marker of activated CTLs that mediates target-cell apoptosis, as well as autoantigen activation and consequent initiation and propagation of autoimmunity. Here, we describe detailed genetic analyses of the GZMB region of chromosome 14q12 to identify genetic variation potentially causal for GV, implicating two non-synonymous SNPs in strong linkage disequilibrium that comprise part of a common multi-variant high-risk haplotype, rs8192917-C— rs11539752-C (55R-94A). To identify possible uncommon deleterious variants that might “hitchhike” on the high-risk haplotype, we then carried out “next-generation” DNA re-sequencing of GZMB in 114 EUR GV patients. Overall, our findings support a direct causal role for the GZMB rs8192917-C—rs11539752-C haplotype (55R-94A) in the pathogenesis of GV.
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634907/
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