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Association of genetic variations in PTPN2 and CD122 with ocular Behcet’s disease
  1. Qi Zhang1,
  2. Hua Li2,
  3. Shengping Hou1,
  4. Hongsong Yu1,
  5. Guannan Su1,
  6. Bolin Deng1,
  7. Jian Qi1,
  8. Chunjiang Zhou1,
  9. Aize Kijlstra3,
  10. Peizeng Yang1
  1. 1Ophthalmology Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, People’s Republic of China
  2. 2Ophthalmology Department, Yongchuan Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
  3. 3University Eye Clinic Maastricht, Maastricht, The Netherlands
  1. Correspondence to Dr Peizeng Yang, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, and Chongqing Eye Institute, Chongqing 400016, People’s Republic of China; peizengycmu{at}


Background Protein tyrosine phosphatases (PTPs) play critical roles in human autoimmunity. Previous studies found that PTPN2 may be the key regulatory factor in the T-cell-mediated immune response. PTPN2 regulates the Janus kinase/signal transducers and activators of transcription pathway by inhibiting signalling via the interleukin (IL)-2 receptor (CD122). An association between genetic variations in PTPN2 and CD122 with ocular Behcet’s disease (BD) has not yet been addressed and was therefore the purpose of this study.

Methods A two-stage case–control study was performed in 906 patients with ocular BD and 2178 healthy controls. Genotyping analysis of 11 single nucleotide polymorphisms was carried out. The expression of PTPN2 in peripheral blood mononuclear cells (PBMCs) was quantified by real-time PCR and cytokine production was measured by ELISA.

Results The frequency of the GG genotype of PTPN2-rs7234029 was significantly lower in patients with ocular BD (p=1.94×10−5, pc=8.34×10−4, OR=0.466). Stratification according to gender showed that rs7234029 was significantly associated with BD in men. A stratified analysis according to the main clinical features showed that rs7234029 was significantly associated with genital ulcers, skin lesions and a positive pathergy test. No association could be detected between BD and CD122 gene polymorphisms. Functional studies showed that rs7234029 GG genotype carriers had a higher PNPT2 mRNA expression level than those which carrying the AA or AG genotype, and a decreased secretion of IL-17 and tumour necrosis factor-alpha was seen by PBMCs from GG carriers. No significant difference could be detected concerning IL-1β or IL-6 production by stimulated PBMCs between the different genotype groups.

Conclusions This study shows that a PTPN2-rs7234029 polymorphism is associated with ocular BD and is strongly influenced by gender. In addition, our results suggest that the genetic association with PTPN2 may involve the regulation of PTPN2 mRNA expression and cytokine secretion.

  • genetics
  • immunology
  • inflammation

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  • QZ and HL contributed equally.

  • Contributors PY, QZ and HL: take responsibility for the integrity of the data and the accuracy of the data analysis. QZ and HL: study concept and design; drafting of the manuscript. All authors: acquisition, analysis or interpretation of data; critical revision of the manuscript for important intellectual content. SH, HY and GS: statistical analysis.

  • Funding This work was supported by National Key R&D Program of China (grant no. 2016YFC0904000), Natural Science Foundation Major International (Regional) Joint Research Project (81320108009), National Natural Science Foundation Project (81300754, 81400389, 31370893), Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003), National Key Clinical Specialties Construction Program of China, Chongqing Science & Technology Platform and Base Construction Program (cstc2014pt-sy10002), Research fund for Traditional Chinese Medicine of Chongqing Health and Family Planning Commission (ZY201401013), Project of Health Bureau of Chongqing (2016MSXM003) and Chongqing applied basic research projects and cutting-edge technology (cstc2014jcyjA10111).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The protocol was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (Permit Number: 2009-201008).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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