Evidence of cis-acting regulatory variation in PTPN22 in patients with rheumatoid arthritis.
OBJECTIVE
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 (p(corrected) < 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.
Oxford University Institute of Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, UK.
P
P
Harrison
L
L
Southam
K
K
Chapman
R
R
Locklin
A
A
Sabokbar
B P
BP
Wordsworth
J J
JJ
Pointon
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*
C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22