A genome-wide association study identifying the SNPs predictive of rapid joint destruction in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common chronic autoimmune disease leading to joint destruction. The aim of the present study was to identify the genomic factors predictive of susceptibility to joint destruction in patients with RA by performing a genome-wide association study of genetic variants, including single nucleotide polymorphisms (SNPs). The study sample included 228 patients with a diagnosis of RA in the past 5 years. Patients were classified into rapid (total Sharp score/years of RA, ≥50) and slow (total Sharp score/years of RA, <50) joint destruction groups for analysis. The association between the genome-wide SNP analysis and joint destruction was evaluated. The following SNPs were strongly associated with rapid radiographic joint destruction: rs2295926 (P<1x10-7), belonging to the N-acetylgalactosaminyltransferase 12 (GALNT12) gene and rs11958855 (P<1x10-6), belonging to the KCNN2 gene (associated with the potassium calcium-activated channel subfamily). The identification of genetic predictors of rapid joint destruction in RA (GALNT12 and KCNN2) may provide information regarding potential therapeutic targets, and this information may be used to assist in the management RA disease progression, thereby improving the functional outcomes for patients.

32 Japanese ancestry rapid joint destruction individuals, 208 Japanese ancestry slow joint destruction individuals