Abstract

Objective: BAK1 is a Bcl-2 family proapoptotic member suggested as a candidate gene for autoimmune diseases. We studied the influence of BAK1 polymorphisms on the risk to develop autoimmune rheumatic diseases (AIRDs) in women.

Methods: A total of 719 Colombian women were included: 209 had systemic lupus erythematosus, 99 primary Sjögren’s syndrome, 159 rheumatoid arthritis and 252 were healthy matched controls. Tag single nucleotide polymorphisms (SNPs) and potentially functional variants were typed by TaqMan® allele discrimination assays. HLA-DRB1 and -DQB1 typing was done by reverse dot-blot hybridization and linkage disequilibrium (LD) with BAK1 SNPs was assessed.

Results: SNPs rs513349 [OR=0.57(0.46-0.72), p=8.57×10^-7] and rs5745582 [OR=1.61(1.26-2.04), p=1.08×10^-4] were associated with the AIRDs included in this study. There was a significant increase of the rs513349G-rs561276C-rs5745582A (GCA) haplotype in each patient cohort as compared to controls [OR=1.95(1.50-2.54), p=2.38×10^-5]. These SNPs were not in LD with HLA-DRB1 or -DQB1 genes.

Conclusions: Our results indicate that the BAK1 polymorphisms influence the risk of acquiring AIRDs in the population studied and are consistent with the paradigm that autoimmune diseases are likely to share common susceptibility variants.