Session Title: Genetics and Genomics of Rheumatic Disease I
Session Type: Abstract Submissions (ACR)
Background/Purpose: Since it is important to explore genetic variations associated with rheumatoid arthritis (RA), genome-wide association studies (GWAS) have led to the identification of RA genetic variants putatively associated with susceptibility. Recently, copy number variation (CNV) may also affect susceptibility to diseases, which have been already observed in diverse autoimmune diseases. Protein tyrosine phosphatase receptor D (PTPRD) is a member of the receptor-like PTP which expresses in the B cell lines and thymus and could be involved in the pathogenesis of autoimmune diseases. In this study, we investigated whether the variation of the PTPRD gene copy number related with susceptibility to RA.
Methods: To investigate whether the variation of the PTPRD gene copy number influence the pathogenesis to RA, blood samples and clinical records were obtained from 217 RA patients (184 females, 33 males) and 205 healthy controls. The genomic DNA of RA patients and healthy controls was extracted from leukocytes in peripheral blood using the Genomic DNA Extraction kit (iNtRON Biotechnology, Korea). To measuring the copy number of PTPRD gene, the quantitative real-time PCR (QPCR) was carried out using Mx3000P QPCR system (Stratagene, La Jolla, CA) and each sample for each gene was assayed in triplicate. Western blot was conducted to detect expression levels of PTPRD
Results: The copy number of PTPRD gene in RA patients was compared with that in healthy controls. The proportion of the individuals with <2 copy of VPREB1 was significantly higher in patients than in controls, while that of the individuals with >2 copy was lower in patients than in controls. The average relative copy number of the PTPRD gene in RA patients (1.14, 95 % CI (1.12-1.16)) was significantly lower than that in healthy controls (1.65, 95 % CI (1.12-1.16), p < 0.0001). Furthermore, we also investigated association between copy number of PTPRD and RA phenotype such as RF factor and anti-CCP levels, which showed no association between copy number of PTPRD and both RA phenotypes. Western blot showed the lower expression of PTPRD in patients with RA compared to control subjects .
Conclusion: This is the first evidence showing the association between low copy number of the PTPRD gene and susceptibility to RA, which may help understanding the pathogenesis of RA and other autoimmune disorders like affecting maturation and differentiation of T cell and B cells.
S. J. Yoo,
M. K. Lim,
I. S. Yoo,
S. W. Kang,
S. C. Shim,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-potential-role-of-protein-tyrosine-phosphatase-receptor-d-ptprd-gene-copy-number-variation-in-susceptibility-to-rheumatoid-arthritis/