the balance of expression of ptpn22 splice forms is significantly different in rheumatoid arthritis patients compared with controlsptpn22拼接的表达形式的平衡与控制相比,风湿性关节炎患者明显不同.pdf

Ronninger et al. Genome Medicine 2012, 4:2 /content/4/1/2 RESEARCH Open Access The balance of expression of PTPN22 splice forms is significantly different in rheumatoid arthritis patients compared with controls 1*† 2† 1 3 4 4 Marcus Ronninger , Yongjing Guo , Klementy Shchetynsky , Andrew Hill , Mohsen Khademi , Tomas Olsson , 3 1 2 2 2 Padmalatha S Reddy , Maria Seddighzadeh , James D Clark , Lih-Ling Lin , Margot O’Toole and Leonid Padyukov1 Abstract Background: The R620W variant in protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with rheumatoid arthritis (RA). The PTPN22 gene has alternatively spliced transcripts and at least two of the splice forms have been confirmed to encode different PTPN22 (LYP) proteins, but detailed information regarding expression of these is lacking, especially with regard to autoimmune diseases. Methods: We have investigated the mRNA expression of known PTPN22 splice forms with TaqMan real-time PCR in relation to ZNF592 as an endogenous reference in peripheral blood cells from three independent cohorts with RA patients (n = 139) and controls (n = 111) of Caucasian origin. Polymorphisms in the PTPN22 locus (25 SNPs) and phenotypic data (gender, disease activity, ACPA and RF status) were used for analysis. Additionally, we addressed possible effects of methotrexate treatment on PTPN22 expression. Results: We found consistent differences in the expression of the PTPN22 splice forms in unstimulated peripheral blood mononuclear cells between RA patients and normal controls. This difference was more pronoun