Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC

Abstract

We conducted a genome-wide association study of generalized vitiligo in the Chinese Han population by genotyping 1,117 cases and 1,429 controls. The 34 most promising SNPs were carried forward for replication in samples from individuals of the Chinese Han (5,910 cases and 9,916 controls) and Chinese Uygur (713 cases and 824 controls) populations. We identified two independent association signals within the major histocompatibility complex (MHC) region (rs11966200, Pcombined=1.48x10(-48), OR=1.90; rs9468925, Pcombined=2.21x10(-33), OR=0.74). Further analyses suggested that the strong association at rs11966200 might reflect the reported association of the HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles and that the association at rs9468925 might represent a previously unknown HLA susceptibility allele. We also identified one previously undescribed risk locus at 6q27 (rs2236313, Pcombined=9.72x10(-17), OR=1.20), which contains three genes: RNASET2, FGFR1OP and CCR6. Our study provides new insights into the genetic basis of vitiligo.

Ulcerative colitis associated with vitiligo and IgA deficiency in a young girl

“…It is also possible to encounter a series of autoimmune diseases, such as bullous epidermolysis, vitiligo and/or psoriasis. Some authors consider that vitiligo pathogenesis associated with IBD is autoimmune or, in other cases, genetic [10,11]. The incidence of vitiligo in the general population is 0.3%, with a significantly lower rate compared to its 1.1% incidence among UC patients [6,12].…”

ANKRD55 and DHCR7 are novel multiple sclerosis risk loci

“…6,9 Further evidence for the generalized involvement of the CCR6 gene region in autoimmune disease risk comes from two independent GWAS on vitiligo each of which identified strongly associated SNPs located 30 --175 kb upstream from CCR6. 10,11 The CYP2R1 and DHCR7 loci reached genome-wide significance in two GWAS on vitamin D insufficiency. 12,13 CYP2R1 rs10741657 and DHCR7 rs12785878 were found to be associated with T1D, a condition associated with vitamin D deficiency.…”

The Pathogenesis of Vitiligo

“…When this gene is overexpressed, it makes cells more vulnerable to oxidative stress (Thompson et al, 2009), an important mechanism for melanocyte destruction. The two genes are FGFR10P, which encodes a fibroblast growth factor receptor and can play a role in cell cycle progression in some disorders (Acquaviva et al, 2009), and the chemokine receptor 6 gene (CCR6) (Quan et al, 2010). Another HLA-oriented study by de Castro et al (2010) examined the gene encoding the discoidin domain receptor 1 (DDR1).…”

“…Overall, these candidate associations with NSV support the assertion that NSV susceptibility loci are shared with loci associated with other autoimmune diseases (Ying et al, 2010). In another genome-wide association study, susceptibility loci were found on chromosome 6 and in the MHC (Quan et al, 2010). Genotyping of 6,623 vitiligo patients and 10,740 controls was carried out, and analyzed for 34 SNPs which deemed promising from a www.intechopen.com…”