The PTPN22 is a negative regulator of the T cell response. Its +1858C>T (R620W) polymorphism has been shown to associate with a risk for multiple autoimmune diseases, including type 1 diabetes (T1D) and juvenile idiopathic arthritis (JIA). The minor (susceptibility) allele is absent in Asian populations, but a recent study suggested an independent involvement of another polymorphism located within the promoter -1123 nucleotides relative to the translational start site.
We aimed to analyse the association of three PTPN22 polymorphisms in two distinct Caucasian populations, the Czechs (with T1D and with JIA) and Azeri (with T1D).
The single nucleotide polymorphisms (SNP) at positions -1123 (rs2488457), +1858 (rs2476601, the R620W substitution), and +2740 (rs1217412) were genotyped using TaqMan assays in 372 subjects with childhood-onset T1D, 130 subjects with JIA, and 400 control subjects of Czech origin, and in 160 subjects with T1D and 271 healthy controls of Azeri origin.
In the Czechs, all three SNPs were in a tight linkage disequlibrium, while in the Azeri, the linkage disequlibrium was limited to between the promoter and 3'-UTR polymorphism, D'(-1123, +2740)=0.99, r(2)=0.72. Haplotype reconstruction via the expectation-maximization algorithm showed in both populations that only the haplotype containing the minor (W) allele at codon 620 was associated with T1D (OR=2.26, 95% CI 1.68-3.02 in Czechs, OR=14.8, 95% CI 2.0-651 in Azeri) or JIA (OR=2.43, 95% CI 1.66-3.56 in Czechs). The haplotypes having the wild-type (R) allele at codon 620 and minor alleles at -1123 and/or +2740 were neutral as to the risk of autoimmune conditions in both populations.
In two different Caucasian populations, the Czechs and the Azeri, no independent contribution can be detected either of the -1123 promoter SNP or the +2740 3'-UTR SNP, and only the minor allele at PTPN22 codon 620 contributes to the risk of autoimmunity.