Bela Melegh (University of Pécs, Hungary) and team explain that PTPN22 is expressed in lymphocytes and is a known susceptibility loci for autoimmune disorders. The C1858T substitution in PTPN22 results in an arginine-to-tryptophan change and affects intracellular protein binding.
The C1858T variant has been associated with the risk for various disorders, say the authors, including Type 1 diabetes, systemic lupus erythematosus, and Grave’s disease. It has also been associated with RA but only in patients who were positive for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibody.
In this study, Melegh’s team genotyped 399 patients with RA and 107 healthy controls matched for age and gender. All controls were negative for RF and anti-CCP.
The 1858T allele was significantly more prevalent in RA patients than in controls (24.4% vs 11.2%), the authors report. The TC genotype was also more common in RA patients versus controls (30.3% vs 18.7%).
This was true in both the overall RA population and among RA patients seropositive for RF and/or anti-CCP antibody.
In multivariate analysis, the T allele was associated with a 2.48-fold increased risk for RA after adjusting for age and gender. There was also evidence for a gene dosage effect, with individuals homozygous for the T allele having a 5.04-fold increased risk.
“The data presented here show that in the Hungarians the C1858T variants of PTPN22 represent susceptibility for the disease mainly in seropositive patients, and the association is gene dosage dependent,” Melegh et al conclude.
Noting that the contemporary Hungarian population shows the main genetic characteristics of the average European populations, they add: “Therefore, the Hungarian population samples are similar to the British, French, Swedish, and North American populations even if individuals with Asian origin might be present in low percentage rates in the Hungarian RA population samples.”