title: Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.
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.
authors.affiliation: Human Medical Genetics Program, School of Medicine, University of Colorado, P.O. Box 6511, Mailstop 8300, Aurora, CO 80045, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.forename: Stanca A
authors.initials: SA
authors.lastname: Birlea
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Fain
authors.forename: Katherine
authors.initials: K
authors.lastname: Gowan
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Riccardi
authors.forename: Paulene J
authors.initials: PJ
authors.lastname: Holland
authors.forename: Christina M
authors.initials: CM
authors.lastname: Mailloux
authors.forename: Alexandra J D
authors.initials: AJ
authors.lastname: Sufit
authors.forename: Saunie M
authors.initials: SM
authors.lastname: Hutton
authors.forename: Anita
authors.initials: A
authors.lastname: Amadi-Myers
authors.forename: Dorothy C
authors.initials: DC
authors.lastname: Bennett
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wallace
authors.forename: Wayne T
authors.initials: WT
authors.lastname: McCormack
authors.forename: E Helen
authors.initials: EH
authors.lastname: Kemp
authors.forename: David J
authors.initials: DJ
authors.lastname: Gawkrodger
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Weetman
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Leone
authors.forename: Alain
authors.initials: A
authors.lastname: Taïeb
authors.forename: Thomas
authors.initials: T
authors.lastname: Jouary
authors.forename: Khaled
authors.initials: K
authors.lastname: Ezzedine
authors.forename: Nanny
authors.initials: N
authors.lastname: van Geel
authors.forename: Jo
authors.initials: J
authors.lastname: Lambert
authors.forename: Andreas
authors.initials: A
authors.lastname: Overbeck
authors.forename: Richard A
authors.initials: RA
authors.lastname: Spritz
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008545:Melanoma / Q000235:genetics; D014442:Monophenol Monooxygenase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014820:Vitiligo / Q000235:genetics* / Q000276:immunology
chemical_list: D005819:Genetic Markers; D014442:Monophenol Monooxygenase
references.citation: J Eur Acad Dermatol Venereol. 2007 Feb;21(2):205-13
references.pmid: 17243956
references.citation: Int J Cancer. 2004 Feb 10;108(4):571-9
references.pmid: 14696122
references.citation: Semin Immunol. 2006 Aug;18(4):214-23
references.pmid: 16731003
references.citation: Clin Endocrinol (Oxf). 2007 Apr;66(4):508-12
references.pmid: 17371467
references.citation: Curr Opin Genet Dev. 2003 Jun;13(3):284-9
references.pmid: 12787791
references.citation: Nat Genet. 2008 Jul;40(7):886-91
references.pmid: 18488027
references.citation: Nat Rev Genet. 2009 May;10(5):318-29
references.pmid: 19373277
references.citation: Arthritis Rheum. 2008 Aug;58(8):2275-86
references.pmid: 18668548
references.citation: Nat Genet. 2009 Aug;41(8):920-5
references.pmid: 19578364
references.citation: Semin Immunol. 2009 Dec;21(6):363-71
references.pmid: 19447046
references.citation: Diabetes. 2008 Oct;57(10):2858-61
references.pmid: 18647951
references.citation: Pigment Cell Res. 2003 Jun;16(3):208-14
references.pmid: 12753387
references.citation: Curr Dir Autoimmun. 2008;10:244-57
references.pmid: 18460890
references.citation: J Dermatol. 1997 Sep;24(9):561-3
references.pmid: 9350100
references.citation: Diabetes. 2009 Apr;58(4):1007-17
references.pmid: 19168599
references.citation: Hum Mol Genet. 2009 Nov 1;18(21):4195-203
references.pmid: 19648290
references.citation: BMC Med Genet. 2009 Mar 05;10:22
references.pmid: 19265545
references.citation: Am J Hum Genet. 2008 Feb;82(2):453-63
references.pmid: 18252225
references.citation: Genet Epidemiol. 2004 Jan;26(1):61-9
references.pmid: 14691957
references.citation: Cell Growth Differ. 2001 Apr;12(4):201-10
references.pmid: 11331249
references.citation: Nucl Recept Signal. 2008;6:e009
references.pmid: 19043594
references.citation: Pigment Cell Melanoma Res. 2008 Apr;21(2):162-71
references.pmid: 18426409
references.citation: J Immunol. 2009 Apr 15;182(8):4830-5
references.pmid: 19342661
references.citation: J Eur Acad Dermatol Venereol. 2007 Aug;21(7):865-76
references.pmid: 17658994
references.citation: Nat Genet. 2008 Dec;40(12):1399-401
references.pmid: 18978792
references.citation: Am J Hum Genet. 2002 Jan;70(1):124-41
references.pmid: 11719900
references.citation: Gene Expr. 1991 May;1(2):103-10
references.pmid: 1820207
references.citation: Nature. 2007 Oct 18;449(7164):851-61
references.pmid: 17943122
references.citation: Arthritis Rheum. 2009 Jan;60(1):251-7
references.pmid: 19116909
references.citation: Biochem J. 2001 Apr 15;355(Pt 2):259-69
references.pmid: 11284711
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: N Engl J Med. 2007 Aug 30;357(9):851-62
references.pmid: 17660530
references.citation: Theor Popul Biol. 2001 Nov;60(3):155-66
references.pmid: 11855950
references.citation: Nat Genet. 2006 Oct;38(10):1166-72
references.pmid: 16998491
references.citation: Nat Genet. 2006 Aug;38(8):904-9
references.pmid: 16862161
references.citation: Pigment Cell Res. 2007 Feb;20(1):27-35
references.pmid: 17250545
references.citation: Pigment Cell Res. 2006 Feb;19(1):51-7
references.pmid: 16420246
references.citation: Immunity. 2006 Aug;25(2):237-47
references.pmid: 16901729
references.citation: Am J Hum Genet. 2005 May;76(5):773-9
references.pmid: 15776395
references.citation: Curr Opin Immunol. 2003 Oct;15(5):533-43
references.pmid: 14499262