rs33996649

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 is a research highlight discussing PTPN22 splice forms and their role in rheumatoid arthritis. The paper reviews findings that RA patients show altered expression ratios of PTPN22 isoforms (LYP_v1 and LYP_v2) in peripheral blood mononuclear cells compared to healthy controls, with the LYP_v1/LYP_v2 ratio significantly elevated in RA. The R620W variant (rs2476601) and R263Q variant (rs33996649) in PTPN22 are associated with autoimmune disease susceptibility, with the W620 allele increasing RA risk.

This study evaluated two PTPN22 coding variants (R263Q and R620W) in inflammatory bowel disease using case-control analysis and meta-analysis. The R263Q variant (rs33996649) showed association with reduced UC risk (pooled OR=0.69, 95% CI 0.51-0.93, P=0.013) but not CD. The R620W variant (rs2476601) was associated with reduced CD risk (pooled OR=0.81, 95% CI 0.75-0.89, P=7.4E-06) but not UC, demonstrating differential effects of these two autoimmunity-associated variants on CD versus UC.