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A functional variant of PTPN22 confers risk for Vogt-Koyanagi-Harada syndrome but not for ankylosing spondylitis.

Zhang Q, Qi J, Hou S, Du L, Yu H, Cao Q, Zhou Y, Liao D, Kijlstra A, Yang P - PLoS ONE (2014)

Bottom Line: No significant association of the tested SNPs with AAU+AS+ patients was observed.Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively).No significant association was observed concerning T cell activation and rs2488457 genotype.

View Article: PubMed Central - PubMed

Affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.

ABSTRACT

Background: Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS).

Methods: A total of 1005 VKH syndrome, 302 AAU+AS+ patients and 2010 normal controls among the Chinese Han population were enrolled in the study. Genotyping, PTPN22 expression, cell proliferation, cytokine production and cell activation were examined by PCR-RFLP, Real-time PCR, CCK8, ELISA and Flow cytometry.

Results: The results showed significantly increased frequencies of the rs2488457 CC genotype and C allele but a decreased frequency of the GG genotype in VKH syndrome patients (PBonferroni correction (Pc) = 3.47×10(-7), OR = 1.54; Pc = 3.83×10(-8), OR = 1.40; Pc = 6.35×10(-4), OR = 0.62; respectively). No significant association of the tested SNPs with AAU+AS+ patients was observed. Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively). No significant association was observed concerning T cell activation and rs2488457 genotype.

Conclusions: The study showed that a functional variant of PTPN22 confers risk for VKH syndrome but not for AAU+AS+ in a Chinese Han population, which may be due to a modulation of the PTPN22 expression, PBMC proliferation and IL-10 production.

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The influence of rs2488457 on the mRNA expression of PTPN22.The mRNA expression of PTPN22 in PBMCs from normal controls carrying different genotypes of rs2488457 (CC = 18, CG = 31, GG = 9). Data are represented as the mean ± SD.
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pone-0096943-g001: The influence of rs2488457 on the mRNA expression of PTPN22.The mRNA expression of PTPN22 in PBMCs from normal controls carrying different genotypes of rs2488457 (CC = 18, CG = 31, GG = 9). Data are represented as the mean ± SD.

Mentions: To investigate whether the expression of PTPN22 was affected by the different genotypes of rs2488457 we performed the following experiments. PBMCs were isolated for PTPN22 detection from 58 unrelated genotyped healthy individuals (CC = 18, CG = 31, GG = 9). Our results showed a significantly decreased expression of PTPN22 in CC cases compared to CG and GG cases (Figure 1. Pc = 0.015; Pc = 0.009, respectively).


A functional variant of PTPN22 confers risk for Vogt-Koyanagi-Harada syndrome but not for ankylosing spondylitis.

Zhang Q, Qi J, Hou S, Du L, Yu H, Cao Q, Zhou Y, Liao D, Kijlstra A, Yang P - PLoS ONE (2014)

The influence of rs2488457 on the mRNA expression of PTPN22.The mRNA expression of PTPN22 in PBMCs from normal controls carrying different genotypes of rs2488457 (CC = 18, CG = 31, GG = 9). Data are represented as the mean ± SD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016172&req=5

pone-0096943-g001: The influence of rs2488457 on the mRNA expression of PTPN22.The mRNA expression of PTPN22 in PBMCs from normal controls carrying different genotypes of rs2488457 (CC = 18, CG = 31, GG = 9). Data are represented as the mean ± SD.
Mentions: To investigate whether the expression of PTPN22 was affected by the different genotypes of rs2488457 we performed the following experiments. PBMCs were isolated for PTPN22 detection from 58 unrelated genotyped healthy individuals (CC = 18, CG = 31, GG = 9). Our results showed a significantly decreased expression of PTPN22 in CC cases compared to CG and GG cases (Figure 1. Pc = 0.015; Pc = 0.009, respectively).

Bottom Line: No significant association of the tested SNPs with AAU+AS+ patients was observed.Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively).No significant association was observed concerning T cell activation and rs2488457 genotype.

View Article: PubMed Central - PubMed

Affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.

ABSTRACT

Background: Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS).

Methods: A total of 1005 VKH syndrome, 302 AAU+AS+ patients and 2010 normal controls among the Chinese Han population were enrolled in the study. Genotyping, PTPN22 expression, cell proliferation, cytokine production and cell activation were examined by PCR-RFLP, Real-time PCR, CCK8, ELISA and Flow cytometry.

Results: The results showed significantly increased frequencies of the rs2488457 CC genotype and C allele but a decreased frequency of the GG genotype in VKH syndrome patients (PBonferroni correction (Pc) = 3.47×10(-7), OR = 1.54; Pc = 3.83×10(-8), OR = 1.40; Pc = 6.35×10(-4), OR = 0.62; respectively). No significant association of the tested SNPs with AAU+AS+ patients was observed. Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively). No significant association was observed concerning T cell activation and rs2488457 genotype.

Conclusions: The study showed that a functional variant of PTPN22 confers risk for VKH syndrome but not for AAU+AS+ in a Chinese Han population, which may be due to a modulation of the PTPN22 expression, PBMC proliferation and IL-10 production.

Show MeSH
Related in: MedlinePlus