Association Analysis of Genes of the IL19 Cluster and Their Receptors in Vitiligo Patients
Association Analysis of Genes of the IL19 Cluster and Their Receptors in Vitiligo Patients
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DOI：
10.1159/000317526
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发表时间：
2010-01-01
期刊：
影响因子：
3.4
通讯作者：
Koks, Sulev
中科院分区：
文献类型：
--
作者：
Kingo, Kuelli;Reimann, Ene;Koks, Sulev
本研究的目的是探讨白细胞介素（IL）19、IL-20、IL-24和IL-20受体I型（IL-20-RI）的两条链IL-20 RA和IL-20 RB（分别位于染色体1 q32、6 q22 -23和3q 22）的编码基因是否与白癜风相关。该研究涉及76名白癜风患者和236名无关的健康志愿者。从全血中提取基因组DNA，用四引物扩增突变系统聚合酶链反应分析20个单核苷酸多态性的频率。与对照相比，白癜风患者中IL 19 rs 2243188的次要等位基因显著增加（53.3%对28.6%，校正的p < 0.0001）。单倍型分析揭示了2种IL 19/IL 20扩展单倍型（AACGTAA和ACCGTAA）和2种IL 20 RB单倍型（AGTA和AGGA）与白癜风的相关性，在多次测试校正后仍显着。IL 19 rs 2243188位的A-至-C交换导致核受体亚家族2因子结合位点的丧失，该结合位点被认为影响小鼠海马发育和神经元分化。IL 20 RB单倍型的第三个位置由rs747842占据，其诱导干扰素调节因子4结合位点的丧失，所述干扰素调节因子4结合位点在先天性和适应性免疫的调节中以及在色素沉着的信号传导中具有重要作用。总之，本研究首次描述了IL 19簇及其受体基因多态性与白癜风之间的关联，表明IL 19及其受体基因IL 20 RB在疾病发病机制中的作用。版权所有（C）2010 S. Karger AG，巴塞尔
The aim of the present study was to explore whether the genes encoding interleukin (IL) 19, IL-20, IL-24 and 2 chains of the IL-20 receptor type I (IL-20-RI), IL-20RA and IL-20RB, located on chromosomes 1q32, 6q22-23 and 3q22, respectively, are associated with vitiligo. The study involved 76 patients with vitiligo and 236 unrelated healthy volunteers. Genomic DNA was extracted from the whole blood and the frequencies of 20 single nucleotide polymorphisms were analysed by tetraprimer amplification refractory mutation system polymerase chain reaction. The minor allele of IL19 rs2243188 was significantly increased in vitiligo patients compared to controls (53.3 vs. 28.6%, adjusted p < 0.0001). The haplotype analysis revealed associations of 2 IL19/IL20 extended haplotypes (AACGTAA and ACCGTAA) and 2 IL20RB haplotypes (AGTA and AGGA) with vitiligo, remaining significant after correction for multiple testing. The A-to-C exchange at position IL19 rs2243188 leads to the loss of a nuclear receptor subfamily 2 factor binding site that is thought to influence mouse hippocampal development and neuronal differentiation. The third position of the IL20RB haplotypes is taken by rs747842 that induces the loss of the interferon regulatory factor 4 binding site that has an important role in the regulation of innate and adaptive immunity and in the signalling of pigmentation as well. In conclusion, the present study describes first-time associations between polymorphisms of genes of the IL19 cluster and their receptors and vitiligo, indicative of the part of IL19 and its receptor gene IL20RB in disease pathogenesis. Copyright (C) 2010 S. Karger AG, Basel