Copy number variations and gene polymorphisms of Complement components in ocular Behcet’s disease and Vogt-Koyanagi-Harada syndrome

Dengfeng Xu,Peizeng Yang,Jun Zhang,Yanni Jiang,Aize Kijlstra,Shengping Hou

doi:10.1038/srep12989

Abstract

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.

Highlights

To several mega base pairs in size[9]
The copy number variations of C6, C7, C8A, C8B and C9 displayed no statistical difference in Behcet’s disease (BD) patients and VKH patients compared with controls (Supplementary Table 4)
The present study shows that a high gene copy number of the complement component C3 is a risk factor for BD and VKH syndrome

Summary

Introduction

To several mega base pairs in size[9]. Previous studies have shown that CNV may be closely related to phenotypic variation and play a key role in the evolution and development of species[10]. Whether the CNVs and SNPs of complement C3, C5 and the other downstream complement components that participate in the final pathway of the complement cascade are associated with BD and VKH syndrome has not yet been reported and was the subject of the study reported here. To address this question we analyzed the copy number variations and polymorphisms of C3, C5, C6, C7, C8A, C8B and C9 in two common types of uveitis in China

Methods

Results

Conclusion