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Abstract
Objectives: To assess whether there are cis-regulatory polymorphisms that regulate protein tyrosine phosphatase, non-receptor type 22 (PTPN22) expression in rheumatoid arthritis (RA).
Methods: RNA was extracted from positively selected CD56+, CD8+, and CD4+ mononuclear cells and the ‘residual’ cells from 12 RA patients heterozygous for the PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601). Relative allelic expression was measured by single base extension (SBE) assay.
Results: There was relative differential allelic expression (DAE ≥ 20%) in eight patients (p < 10−5); seven patients demonstrated DAE in more than one cell type; four patients had statistically significant differences between these cell populations (pcorrected < 0.05).
Conclusions: We have demonstrated significant differences in expression of PTPN22 alleles in RA patients, indicating the probable existence of cis-acting regulatory elements.
Acknowledgements
This work was funded by the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, UK. PH was funded by an unrestricted grant from Pfizer. JJP was funded by the NIHR Oxford Musculoskeletal Biomedical Research Unit.