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Predisposition to Behçet’s disease and VKH syndrome by genetic variants of miR-182

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Abstract

Previous studies have identified miR-182, miR-27a, FoxO1, and IL2RA as regulatory factors for Treg cell development and function. In order to investigate the association of miR-182, miR-27a, FoxO1, and IL2RA gene polymorphisms with Behçet’s disease (BD) and Vogt–Koyanagi–Harada (VKH) syndrome in a Chinese Han population, a two-stage association study was performed in 820 BD, 900 VKH patients, and 1,800 controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. In the first stage study, association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 400 BD, 400 VKH patients, and 600 controls. The results showed significantly decreased frequencies of the miR-182/rs76481776 CC genotype and C allele in BD (P = 3.36 × 10−4, OR = 0.55; P = 4.74 × 10−4, OR = 0.59) and VKH patients (P = 1.11 × 10−4, OR = 0.53; P = 1.26 × 10−4, OR = 0.56). No significant association of the other nine SNPs with BD or VKH was observed. In the second stage study, association analysis of miR-182/rs76481776 was performed in 420 BD, 500 VKH patients, and 1,200 controls. The second stage and combined studies confirmed the association of miR-182/rs76481776 with BD (CC genotype: P = 3.25 × 10−7, OR = 0.58; C allele: P = 1.81 × 10−7, OR = 0.60) and VKH (CC genotype: P = 7.89 × 10−8, OR = 0.57; C allele: P = 2.52 × 10−8, OR = 0.59). Real-time PCR analysis showed a significantly increased expression of miR-182 in TT/CT cases compared to CC cases in anti-CD3/CD28 antibodies-stimulated CD4+ T cells (P = 2.1 × 10−2). In conclusion, this study suggests that miR-182, but not miR-27a, FoxO1, and IL2RA, contributes to the genetic susceptibility of BD and VKH.

Key Message

  • MiR-182 contributes to genetic susceptibility of BD and VKH.

  • No significant association of miR-27a, FoxO1, and IL2RA with BD or VKH was observed.

  • Significantly increased expression of miR-182 in TT/CT cases compared to CC cases was observed.

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Acknowledgments

The authors would like to thank all donors enrolled in the present study. This work was supported by Natural Science Foundation Major International (Regional) Joint Research Project (81320108009), National Basic Research Program of China (973 Program) (2011CB510200), Key Project of Natural Science Foundation (81130019), National Natural Science Foundation Project (31370893, 81200678), Basic Research program of Chongqing (cstc2013jcyjC10001), Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003), National Clinical Key Department Construction Program, Key Project of Health Bureau of Chongqing (2012-1-003), and Fund for PAR-EU Scholars Program.

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The authors declare no conflict of interests.

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Authors and Affiliations

  1. The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, 400016, People’s Republic of China

    Hongsong Yu, Yunjia Liu, Lin Bai & Peizeng Yang

  2. University Eye Clinic Maastricht, Maastricht, The Netherlands

    Aize Kijlstra

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  1. Hongsong Yu
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  2. Yunjia Liu
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  3. Lin Bai
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Correspondence to Peizeng Yang.

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Fig. S1

Comparison of the relative expression levels of miR-182 variants. PBMCs and LPS-stimulated PBMCs samples of 12 CC genotype, 12 CT and TT genotype of rs76481776 were freshly obtained from healthy controls in the study (GIF 10 kb)

High resolution image (TIFF 222 kb)

Fig. S2

The influence of various rs76481776 genotypes on expression of FoxO1. Purified CD4+ T cells and anti-CD3/CD28 antibodies-stimulated CD4+ T cells of 12 CC genotypes, 8 CT and TT genotypes of rs76481776 were freshly obtained from healthy controls in the study (GIF 19 kb)

High resolution image (TIFF 115 kb)

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(DOC 220 kb)

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Yu, H., Liu, Y., Bai, L. et al. Predisposition to Behçet’s disease and VKH syndrome by genetic variants of miR-182. J Mol Med 92, 961–967 (2014). https://doi.org/10.1007/s00109-014-1159-9

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  • DOI: https://doi.org/10.1007/s00109-014-1159-9

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