Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo (The New England Journal of Medicine)

N Engl J Med 2010; 362:1686-1697; May 6, 2010; DOI: 10.1056/NEJMoa0908547

BACKGROUND

nejm

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=9.05×10−23) and class II molecules (P=4.50×10−34), PTPN22 (P=1.31×10−7), LPP (P=1.01×10−11),IL2RA (P=2.78×10−9), UBASH3A (P=1.26×10−9), and C1QTNF6(P=2.21×10−16). We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE(P=7.07×10−15) and GZMB (P=3.44×10−8), and in a locus containingTYR (P=1.60×10−18), 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.

Leer el artículo completo en la revista NEJM

Otras referencias del artículo (NIH)

67 artículos citan este artículo

Enviar comentario

Tu dirección de correo electrónico no será publicada. Los campos necesarios están marcados *

Puedes usar las siguientes etiquetas y atributos HTML: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>