rs1893217

This meta-analysis of 22,233 CAD cases and 64,762 controls tested 41 celiac disease-associated SNPs for association with coronary artery disease (CAD). While 58.5% of celiac disease risk alleles showed positive association with CAD (OR 1.001-1.081), this was not significantly different from the 50% expected by chance (p=0.069). Only rs653178 at the SH2B3/ATXN2 locus achieved study-wide statistical significance (OR 1.081, p=2.2×10⁻⁶), likely through pleiotropic effects. The findings provide no convincing evidence that genetic variants associated with celiac disease contribute to CAD risk.

Meta-analysis of 17 studies examining associations between three PTPN2 polymorphisms (rs2542151, rs1893217, rs7234029) and susceptibility to ulcerative colitis and Crohn's disease, involving 18,308 cases and 20,406 controls. The rs2542151 G allele was associated with increased CD risk (OR=1.22, 95% CI 1.15-1.30) and UC risk (OR=1.16, 95% CI 1.07-1.25), with stronger associations in Caucasians than Asians. The rs1893217 C allele showed association with CD (OR=1.45, 95% CI 1.23-1.70), particularly in children (OR=1.56, 95% CI 1.28-1.89), and rs7234029 G allele was associated with CD (OR=1.36, 95% CI 1.16-1.59).

This study identified a novel association between the PTPN2 SNP rs1893217 (intronic variant) and Crohn's disease in a combined German, Swiss, and Polish cohort (343 CD patients, 663 controls). Homozygous carriers of the variant showed significantly increased disease association (OR=2.653, 95% CI=1.147-6.136, P=0.018). Functionally, the variant impaired PTPN2 phosphatase activity, leading to increased MAPK phosphorylation, elevated T-bet expression and IFN-γ secretion in monocytes and impaired autophagosome formation in response to the NOD2 ligand MDP.

This case-control study of 439 Spanish type 1 diabetes (T1D) patients and 861 controls examined the association of PTPN2 polymorphisms with T1D and age at disease onset. The rs2542151*G allele was significantly associated with early-onset T1D (≤16 years) with OR=1.61 (p=0.005) and was linked to earlier disease debut compared to TT homozygotes (mean 16.6 vs 19.1 years, p=0.034), while the rs478582 polymorphism showed no significant association with age at onset.

This case-control association study of juvenile idiopathic arthritis (JIA) in 809 JIA cases and 3,521 controls identified susceptibility loci shared with other autoimmune diseases. Three novel loci were identified: PTPN2 (strongest signals rs7234029, p=7.19×10⁻¹¹, OR=1.59; rs1893217, p=3.48×10⁻⁸, OR=1.52; rs2542151, p=3.05×10⁻⁷, OR=1.45), COG6 (rs7993214, p=3.98×10⁻³, OR=0.79), and ANGPT1 (rs1010824, p=4.93×10⁻³, OR=0.77). Four previously reported JIA loci were confirmed: PTPN22, STAT4, C12orf30, and IL2-IL21. Odds ratios ranged from 1.20 to 1.65 in meta-analysis of initial and independent replication cohorts (n=1,015 cases and 1,568 controls).