Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo.

被引：291

作者：

Jin, Ying ^{[1
,4
]}

Birlea, Stanca A. ^{[1
,3
]}

Fain, Pamela R. ^{[1
,2
,4
,5
]}

Gowan, Katherine ^{[1
]}

Riccardi, Sheri L. ^{[1
]}

Holland, Paulene J. ^{[1
]}

Mailloux, Christina M. ^{[1
]}

Sufit, Alexandra J. D. ^{[1
]}

Hutton, Saunie M. ^{[1
]}

Amadi-Myers, Anita ^{[6
]}

Bennett, Dorothy C. ^{[6
]}

Wallace, Margaret R. ^{[7
]}

McCormack, Wayne T. ^{[8
]}

Kemp, E. Helen ^{[9
]}

Gawkrodger, David J. ^{[10
]}

Weetman, Anthony P. ^{[9
]}

Picardo, Mauro ^{[11
]}

Leone, Giovanni ^{[11
]}

Taieb, Alain ^{[12
]}

Jouary, Thomas ^{[12
]}

Ezzedine, Khaled ^{[12
]}

van Geel, Nanny ^{[13
]}

Lambert, Jo ^{[13
]}

Overbeck, Andreas ^{[14
]}

Spritz, Richard A. ^{[1
,4
]}

机构：

[1] Univ Colorado, Sch Med, Human Med Genet Program, Aurora, CO 80045 USA

[2] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA

[3] Univ Colorado, Sch Med, Dept Dermatol, Aurora, CO 80045 USA

[4] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA

[5] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA

[6] Univ London, Div Basic Med Sci, London, England

[7] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA

[8] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA

[9] Univ Sheffield, Sch Med, Dept Human Metab, Sheffield, S Yorkshire, England

[10] Royal Hallamshire Hosp, Dept Dermatol, Sheffield S10 2JF, S Yorkshire, England

[11] Ist Dermatol S Maria & S Gallicano, Lab Fisiopatol Cutanea, Rome, Italy

[12] Hop St Andre, Dept Dermatol, Ctr Reference Malad Rares Peau, Bordeaux, France

[13] Ghent Univ Hosp, Dept Dermatol, B-9000 Ghent, Belgium

[14] Lumiderm, Madrid, Spain

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 362卷 / 18期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; HAPLOTYPE MAP; GRANZYME-B; DISEASE; RISK; GENE; PIGMENTATION; TYROSINASE; HLA;

D O I：

10.1056/NEJMoa0908547

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 10(sup -23)) and class II molecules (P=4.50 x 10(sup -34)), PTPN22 (P=1.31 x 10(sup -7)), LPP (P=1.01 x 10(sup -11)), IL2RA (P=2.78 x 10(sup -9)), UBASH3A (P=1.26 x 10(sup -9)), and C1QTNF6 (P=2.21 x 10(sup -16)). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07 x 10(sup -15)) and GZMB (P=3.44 x 10(sup -8)), and in a locus containing TYR (P=1.60 x 10(sup -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. N Engl J Med 2010;362:1686-97.

引用

页码：1686 / 1697

页数：12

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