Objective: To analyze whether the polymorphisms -22 (G/C) and -348 (C/T) of the BAT1 gene are associated with susceptibility to rheumatoid arthritis (RA).
Methods: One hundred fifty-six patients with RA and 154 controls were genotyped for HLA-DRB1 and the polymorphisms -22 and -348 of the BAT1 gene.
Results: HLA-DRB1*04 alleles were associated with RA susceptibility (33.9% vs 20.1%; pc = 0.04). Among these, HLA-DRB1*0401 (13.4% vs 5.1%; pc = 0.04) and HLA-DRB1*0404 (5.7% vs 1.2%; pc = 0.2) were increased in patients with RA. Additionally, carriage of BAT1 -348T polymorphism was strongly associated with RA (23.7% vs 12.1%; pc = 0.0002). Significantly, BAT1 -348T was in linkage disequilibrium with HLA-DRB1*0404 and HLA-DRB1*0405. However, BAT1 -348 T was associated independently with HLA-DRB1 shared-epitope alleles (42.6% vs 18.9%; p = 0.001).
Conclusion: The BAT1 -348T polymorphism is associated with RA susceptibility independently of HLA-DRB1. The role of BAT1 in the regulation of tumor necrosis factor-a suggests that BAT1 may regulate the inflammatory response observed in patients with RA.