Copy number variations and gene polymorphisms of complement components in ocular Behcet's disease and Vogt-Koyanagi-Harada syndrome.
Copy number variations and gene polymorphisms of complement components in ocular Behcet's disease and Vogt-Koyanagi-Harada syndrome.
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DOI：
10.1038/srep12989
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发表时间：
2015-08-13
影响因子：
4.6
通讯作者：
Yang P
中科院分区：
文献类型：
--
作者：
Xu D;Hou S;Zhang J;Jiang Y;Kijlstra A;Yang P
补体参与许多免疫介导的疾病。然而，其拷贝数变异（CNVs）和多态性与白塞氏病（BD）和Vogt-Koyanagi-Harada综合征（VKH）的关联尚不清楚。我们通过实时PCR检测拷贝数和mRNA表达。通过ELISA测量基因分型个体中刺激的外周血单核细胞（PBMC）的细胞因子产生。BD和VKH中C3基因拷贝数超过2个的频率显著增加，而C5基因的CNV仅与BD相关。在BD中发现C3 rs 408290和C5 rs 2269067 GG基因型频率增加。未观察到C3和C5 SNP与VKH之间的关联。高CNV组和GG组C3、C5基因型的mRNA表达明显高于其他基因型。在高CNV组和C3 GG基因型病例中观察到IL-17和IFN-γ升高。IL-17在高CNV组和C5 GG基因型病例中升高，而IFN-γ无升高。未观察到C3或C5遗传变异体对TNF-α、IL-10、IL-1β、MCP-1、IL-6和IL-8的产生的影响。因此，我们的研究为补体在葡萄膜炎发病机制中的作用提供了进一步的证据。
Complement is involved in many immune-mediated diseases. However, the association of its copy number variations (CNVs) and polymorphisms with Behcet’s disease (BD) and Vogt-Koyanagi-Harada syndrome (VKH) is unknown. We examined copy number and mRNA expression by real-time PCR. Cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) in genotyped individuals was measured by ELISA. The frequencies of having more than two copies of C3 were significantly increased in BD and VKH, whereas CNV of C5 was only associated with BD. Increased frequencies of the GG genotype of C3 rs408290 and C5 rs2269067 were found in BD. No association was observed between C3 and C5 SNPs and VKH. mRNA expression in the high CNV group and GG cases of C3 and C5 was significantly higher compared to other genotypes. Increased interleukin-17 and IFN-γ was observed in the high CNV group and GG genotype cases of C3. Interleukin-17 but not IFN-γ was increased in the high CNV group and GG genotype cases of C5. No effect of C3 or C5 genetic variants was seen on the production of TNF-α, IL-10, IL-1β, MCP-1, IL-6 and IL-8. Our study thus provides further evidence for a role of complement in the pathogenesis of uveitis.