We set out to determine whether the 1858T allele of PTPN22 was associated with PAD or with autoimmunity in the context of PAD.
We genotyped rs2476601 (g.1858C>T), a single nucleotide polymorphism encoding substitution of arginine for tryptophan in PTPN22 (R620W), in 193 patients with PAD and 148 control subjects from an Australian cohort. We also performed a subgroup analysis according to the presence of autoimmunity and B-cell phenotypes.
C/T and T/T PTPN22 genotypes were more common in patients with PAD than in the matched control subjects (C/T, 18.1 % vs 9.5 % ; T/T, 1.04 % vs 0.6 % ). The T allele was associated with an increased risk of PAD relative to control subjects (odds ratio, 2.10; 95 % CI, 1.11-4.00). The distribution of genotypes in control subjects was similar to those reported previously and did not deviate significantly from Hardy-Weinberg equilibrium. We found a strong association between the 1858T allele and PAD with coexistent autoimmune diseases. In patients with PAD and autoimmunity, 16 (43.2 % ) of 37 had at least one T allele of PTPN22 compared with 27 (17.3 % ) of 156 with the C/C genotype (P?= .0014; odds ratio, 3.64; 95 % CI, 1.68-7.88). We found no evidence that this effect was mediated by enrichment of CD21low B cells.
The 1858T PTPN22 allele is strongly associated with autoimmunity in patients with PAD.