Copy number variants and genetic polymorphisms in TBX21, GATA3, Rorc, Foxp3 and susceptibility to Behcet's disease and Vogt-Koyanagi-Harada syndrome.

Dan Liao,Qingfeng Cao,Shengping Hou,Lin Bai,Aize Kijlstra Aize Kijlstra,Peizeng Yang,Jing Fang,Yunjia Liu,Jun Zhang

doi:10.1038/srep09511

Abstract

This study aimed to investigate the role of genetic variants including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of TBX21, GATA3, Rorc and Foxp3 genes in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. Genotyping of 25 SNPs was performed by iPLEX system (Sequenom) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TaqMan real time PCR was used to assess CNVs. The expression of Rorc and Foxp3 were examined by real-time PCR and cytokine production was measured by ELISA. High Rorc CNV was associated with the susceptibility to BD (P = 8.99 × 10−8, OR = 3.0), and low Foxp3 CNV predisposed to BD in female patients (P = 1.92 × 10−5, OR = 3.1). CNVs for the investigated genes were not altered in VKH syndrome. Further functional studies demonstrated that the relative mRNA expression levels of Rorc were increased in individuals with high Rorc copy number, but not for Foxp3. Increased production of IL-1β and IL-6 was found in individuals carrying a high CNV of Rorc. Our study showed that high CNVs of Rorc and low CNVs of Foxp3 confer risk for BD but not for VKH syndrome. The tested 25 SNPs in TBX21, GATA3, Rorc and Foxp3 did not associate with BD and VKH syndrome.

Highlights

This study aimed to investigate the role of genetic variants including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of TBX21, GATA3, Rorc and Foxp[3] genes in Behcet’s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population
Previous studies found the dysregulations of TBX21/GATA3 and Rorc/Foxp[3] ratios in uveitis patients with neuro-BD20, suggesting that a www.nature.com/scientificreports dysregulated function of these T cell subsets may lead to immune imbalance, proliferation and activation of pathogenic CD41 T cells subsequently leading to uveitis
In this study we show that the frequency of high Rorc CNV was significantly increased in BD, while an increased frequency of low Foxp[3] CNV was found in female BD patients

Summary

Introduction

This study aimed to investigate the role of genetic variants including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of TBX21, GATA3, Rorc and Foxp[3] genes in Behcet’s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. Previous studies found the dysregulations of TBX21/GATA3 and Rorc/Foxp[3] ratios in uveitis patients with neuro-BD20, suggesting that a www.nature.com/scientificreports dysregulated function of these T cell subsets may lead to immune imbalance, proliferation and activation of pathogenic CD41 T cells subsequently leading to uveitis. The association of these four transcriptional factors with BD and VKH syndrome has not yet been addressed and was the aim of our study whereby we explored the association of two genetic variants including CNVs as well as SNPs of TBX21, GATA3, Rorc and Foxp[3] in the pathogenesis of uveitis via a two-stage case control study. No association was found for the tested 25 SNPs of the four genes with BD and VKH syndrome

Objectives

Methods

Results

Conclusion