An in-depth analysis identifies two new independent signals in 11q23.3 associated with vitiligo in the Chinese Han population.

ABSTRACT

BACKGROUND: Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. OBJECTIVE: This study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population. METHODS: We selected and genotyped 26 SNPs at 11q23.3 in an independent cohort including 2924 cases and 4048 controls using the Sequenom MassArray iPLEX® system. Bonferroni adjustment was used for multiple comparisons and P value <1.92×10-3 (0.05/26) was considered statistically significant. RESULTS: The A allele of rs613791 and G allele of rs523604 located in CXCR5 were observed to be significantly associated with vitiligo (OR=1.21, 95% CI 1.11-1.31, P=1.20×10-5; OR=1.14, 95% CI 1.07-1.23, P=1.90×10-4, respectively). The C allele of rs638893 (a previously reported one) located upstream of DDX6 was also significantly associated with vitiligo (OR=1.25, 95% CI 1.12-1.38, P=3.04×10-5). The genotypes distribution of 3 SNPs also showed significant differences between case and control (rs613791 P=7.00×10-6, rs523604 P=4.00×10-3, rs638893 P=1.20×10-5, respectively). The two newly identified SNPs (rs613791 and rs523604) showed independent associations with vitiligo by linkage disequilibrium analysis and conditional logistic regression. CONCLUSIONS: The study identified two new independent signals in the associated locus 11q23.3 for vitiligo. The presence of multiple independent variants emphasizes an important role of this region in disease susceptibility.