Institute of Dermatology and Department of Dermatology at No. 1 Hospital, Anhui Medical University, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China.
Institute of Dermatology and Department of Dermatology at No. 1 Hospital, Anhui Medical University, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China.
J Dermatol Sci. 2017 Oct;88(1):103-109. doi: 10.1016/j.jdermsci.2017.05.001. Epub 2017 May 3.
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.
This study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population.
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 (0.05/26) was considered statistically significant.
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; OR=1.14, 95% CI: 1.07-1.23, P=1.90×10, 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). The genotypes distribution of 3 SNPs also showed significant differences between case and control (rs613791: P=7.00×10, rs523604: P=4.00×10, rs638893: P=1.20×10, respectively). The two newly identified SNPs (rs613791 and rs523604) showed independent associations with vitiligo by linkage disequilibrium analysis and conditional logistic regression.
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.
白癜风是一种自身免疫性疾病，其特征是皮肤色素逐渐丧失，这是由多种因素相互作用引起的，如遗传、免疫和环境等。最近，全基因组关联研究发现 11q23.3 区域的单核苷酸多态性（SNP）rs638893 是白癜风的一个危险因素，该区域的多个 SNP 与其他自身免疫性疾病有关。
本研究旨在鉴定中国汉族人群中 11q23.3 与白癜风相关的其他易感变异。
我们使用 Sequenom MassArray iPLEX 系统，在一个独立的队列中选择并对 11q23.3 中的 26 个 SNP 进行基因分型，该队列包括 2924 例病例和 4048 例对照。采用 Bonferroni 校正进行多重比较，P 值<1.92×10（0.05/26）被认为具有统计学意义。
rs613791 的 A 等位基因和 rs523604 的 G 等位基因位于 CXCR5 中，与白癜风显著相关（OR=1.21，95%CI：1.11-1.31，P=1.20×10；OR=1.14，95%CI：1.07-1.23，P=1.90×10）。DDX6 上游的 rs638893（先前报道的一个 SNP）的 C 等位基因也与白癜风显著相关（OR=1.25，95%CI：1.12-1.38，P=3.04×10）。3 个 SNP 的基因型分布在病例和对照之间也存在显著差异（rs613791：P=7.00×10，rs523604：P=4.00×10，rs638893：P=1.20×10）。通过连锁不平衡分析和条件逻辑回归，这两个新鉴定的 SNP（rs613791 和 rs523604）显示与白癜风具有独立的关联。
本研究在白癜风相关的 11q23.3 区域鉴定到两个新的独立信号。多个独立变异的存在强调了该区域在疾病易感性中的重要作用。
