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Susceptibility Loci Identified for Generalized Vitiligo

Gene study shows links with variants previously associated with other autoimmune diseases

WEDNESDAY, April 21 (HealthDay News) -- There are associations between generalized vitiligo and markers implicating multiple genes, including 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, according to a study published online April 21 in the New England Journal of Medicine.

Ying Jin, M.D., of the University of Colorado School of Medicine in Aurora, and colleagues genotyped 579,146 single-nucleotide polymorphisms (SNPs) in 1,514 generalized vitiligo patients of European-derived white (CEU) ancestry and compared the genotypes with 2,813 CEU controls. In two replication sets -- one comprising 677 independent CEU patients and 1,106 CEU controls, the other comprising 183 CEU simplex trios with generalized vitiligo and 332 CEU multiplex families -- they also tested 50 SNPs.

The researchers found that there were significant associations between generalized vitiligo and SNPs at loci previously associated with other autoimmune diseases, including genes encoding major-histocompatibility-complex class I and class II molecules, PTPN22, LPP, IL2RA, UBASH3A and C1QTNF6. They also found associations between generalized vitiligo and SNPs in two other immune-related loci, RERE and GZMB, and in a locus containing TYR, encoding tyrosinase.

"Vitiligo is associated with the major alleles of SNPs in the TYR region, particularly rs1393350 and the nearby nonsynonymous (R402Q) SNP rs1126809, with which rs1393350 is in tight linkage disequilibrium. The minor alleles of both these SNPs are associated with susceptibility to malignant melanoma, suggesting that susceptibility to TYR-related generalized vitiligo and susceptibility to TYR-related malignant melanoma are mediated by different or perhaps even inverse biologic mechanisms," the authors write.

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