rs2488457

A case-control study of 165 Chinese UC patients and 300 healthy controls examining PTPN22 gene polymorphisms. The -1123G/C variant (rs2488457) showed significant association with UC, with C carriers having higher frequency in patients than controls (66.7% vs 53.3%, OR=1.75, P=0.005) and association with extensive colitis (P=0.029). PTPN22 mRNA levels were elevated in inflamed colonic tissue and correlated with disease activity.

In Chinese Han populations, the PTPN22 promoter polymorphism -1123G>C (rs2488457) is associated with rheumatoid arthritis susceptibility with OR=1.517 (95% CI 1.154-1.995, P=0.003). The well-documented exon 14 variant 1858C>T (rs2476601) and the 788G>A variant (rs33996649) were not polymorphic in this Chinese cohort, suggesting population-specific genetic risk variants for RA.

This genome-wide pathway analysis study identified MSRA (rs10903323) as a novel rheumatoid arthritis susceptibility locus through pathway prioritization of previous GWAS data. In a combined analysis of 1,818 RA patients and 2,498 controls, rs10903323 was associated with RA (P = 3.19 × 10⁻⁴, OR 1.28), while rs12029840 near HIPK1 showed stronger replication (P = 1.64 × 10⁻⁸, OR 1.55). The findings implicate oxidative stress and the MSRA-mediated apoptosis pathway in RA pathogenesis.

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).

A case-control study of 1,123 Korean rheumatoid arthritis patients and 1,008 controls found that genetic variants at PTPN22, TRAF1/C5, 6q23, 4q27, CD40, and CCL21 previously associated with Caucasian RA were not associated with Korean RA. The PADI4 variant rs2240340 showed strong association (p=1.15×10⁻⁸, OR=1.43), demonstrating substantial genetic heterogeneity between ethnic populations.

Case-control study of 381 UK Caucasian idiopathic inflammatory myopathy (IIM) patients and 748 controls examining PTPN22 SNPs. The R620W variant (rs2476601) showed significant association with overall IIM (OR=1.8, p=0.00007) and particularly with polymyositis (OR=2.2, p=0.0001) and juvenile dermatomyositis (OR=2.1, p=0.0006). The association was independent of the HLA 8.1 haplotype.

This review examines slowly progressive type 1 diabetes mellitus (SPIDDM), also known as latent autoimmune diabetes in adults (LADA), discussing its pathogenesis, diagnostic markers, and genetic associations. Key findings include T-cell-mediated insulitis and pseudoatrophic islets characteristic of type 1 diabetes, absence of amyloid deposition seen in type 2 diabetes, and identification of multiple genetic susceptibility loci including HLA haplotypes, PTPN22 rs2476601, INS rs689, CTLA4, TCF7L2 rs7903146, ZMIZ1 rs12571751, SH2B3 rs7310615, and PFKFB3 rs1983890. GAD autoantibodies and HLA genotypes are important risk factors for beta-cell failure progression.