Association Analyses Identify Three Susceptibility Loci for Vitiligo in the Chinese Han Population
Association Analyses Identify Three Susceptibility Loci for Vitiligo in the Chinese Han Population
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关联分析确定中国汉族人群白癜风的三个易感位点
DOI：
10.1038/jid.2012.320
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发表时间：
2013-02-01
影响因子：
6.5
通讯作者：
Zhang, Xue-Jun
中科院分区：
文献类型：
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作者：
Tang, Xian-Fa;Zhang, Zheng;Zhang, Xue-Jun
为了确定白癜风的易感位点，我们对之前的白癜风全基因组关联研究进行了扩展，开展了一项两阶段的重复研究，该研究包含来自中国汉族人群的6857例病例和12025例对照。我们确定了三个易感位点，分别是12q13.2（rs10876864，综合P值 = 8.07×10⁻¹²，优势比（OR）= 1.18）、11q23.3（rs638893，综合P值 = 2.47×10⁻⁹，OR = 1.22）和10q22.1（rs1417210，综合P值 = 1.83×10⁻⁸，OR = 0.88），并且在中国汉族人群中确认了三个之前报道的白癜风位点，即3q28（rs9851967，综合P值 = 8.57×10⁻⁸，OR = 0.88）、10p15.1（rs3134883，综合P值 = 1.01×10⁻⁵，OR = 1.11）和22q12.3（rs2051582，综合P值 = 2.12×10⁻⁵，OR = 1.14）。12q13.2位点中最显著的单核苷酸多态性紧邻PMEL启动子区域的上游，PMEL编码一种主要的黑素细胞抗原，在白癜风皮损皮肤中表达缺失。此外，本研究中确定的12q13.2和11q23.3位点也与其他自身免疫性疾病相关，如1型糖尿病和系统性红斑狼疮。这些发现间接支持了白癜风的发病机制涉及免疫调节因子和黑素细胞特异性因子之间的复杂相互作用。它们还凸显了中国人群和高加索人群中白癜风遗传基础的异同。《皮肤病学研究杂志》（2013年）133卷，403 - 410页；doi:10.1038/jid.2012.320；2012年9月6日在线发表
To identify susceptibility loci for vitiligo, we extended our previous vitiligo genome-wide association study with a two-staged replication study that included 6,857 cases and 12,025 controls from the Chinese Han population. We identified three susceptibility loci, 12q13.2 (rs10876864, P-combined = 8.07 X 10(-12), odds ratio (OR) = 1.18), 11q23.3 (rs638893, P-combined = 2.47 x 10(-9), OR = 1.22), and 10q22.1 (rs1417210, P-combined = 1.83 x 10(-8), OR = 0.88), and confirmed three previously reported loci for vitiligo, 3q28 (rs9851967, P-combined = 8.57 x 10(-8), OR = 0.88), 10p15.1 (rs3134883, P-combined = 1.01 x 10(-5), OR = 1.11), and 22q12.3 (rs2051582, P-combined = 2.12 x 10(-5), OR = 1.14), in the Chinese Han population. The most significant single-nucleotide polymorphism in the 12q13.2 locus is located immediately upstream of the promoter region of PMEL, which encodes a major melanocyte antigen and has expression loss in the vitiligo lesional skin. In addition, both 12q13.2 and 11q23.3 loci identified in this study are also associated with other autoimmune diseases such as type 1 diabetes and systemic lupus erythematosus. These findings provide indirect support that vitiligo pathogenesis involves a complex interplay between immune regulatory factors and melanocyte-specific factors. They also highlight similarities and differences in the genetic basis of vitiligo in Chinese and Caucasian populations. Journal of Investigative Dermatology (2013) 133, 403-410; doi:10.1038/jid.2012.320; published online 6 September 2012