Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo.
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.
Jin
Ying
Y
Human Medical Genetics Program, School of Medicine, University of Colorado, P.O. Box 6511, Mailstop 8300, Aurora, CO 80045, USA.
Birlea
Stanca A
SA
Fain
Pamela R
PR
Gowan
Katherine
K
Riccardi
Sheri L
SL
Holland
Paulene J
PJ
Mailloux
Christina M
CM
Sufit
Alexandra J D
AJ
Hutton
Saunie M
SM
Amadi-Myers
Anita
A
Bennett
Dorothy C
DC
Wallace
Margaret R
MR
McCormack
Wayne T
WT
Kemp
E Helen
EH
Gawkrodger
David J
DJ
Weetman
Anthony P
AP
Picardo
Mauro
M
Leone
Giovanni
G
Taïeb
Alain
A
Jouary
Thomas
T
Ezzedine
Khaled
K
van Geel
Nanny
N
Lambert
Jo
J
Overbeck
Andreas
A
Spritz
Richard A
RA
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
D005819:Genetic Markers; D014442:Monophenol Monooxygenase
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