Objective: Bcl-2 antagonist killer 1 (BAK1) is a Bcl-2 family proapoptotic member suggested as a candidate gene for autoimmune diseases. The influence of BAK1 polymorphisms on the risk of developing autoimmune rheumatic diseases (AIRDs) in women was investigated.
Methods: A total of 719 Colombian women were included in the present study: 209 had systemic lupus erythematosus, 99 primary Sjögren 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 HLA-DQB1 typing was performed by reverse dot-blot hybridisation and linkage disequilibrium (LD) with BAK1 SNPs was assessed.
Results: SNPs rs513349 (odds ratio (OR) 0.57, 95% CI 0.46 to 0.72, p = <0.001) and rs5745582 (OR 1.61, 95% CI 1.26 to 2.04, p = <0.001) 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, 95% CI 1.50 to 2.54, p = <0.001). These SNPs were not in LD with HLA-DRB1 or HLA-DQB1 genes.
Conclusions: The 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.
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▸ Additional data (supplementary tables 1–7 and supplementary information) are published online only at http://ard.bmj.com/content/vol69/issue2
Funding This study was supported by Colciencias, Bogota (2213-04-16715 and 2213-04-16484); TCC Foundation, Medellin, and the School of Medicine, Rosario University, Bogota, Colombia.
Competing interests None declared.
Ethics approval Ethics approval was granted by the Corporacion para Investigaciones Biologicas.
Provenance and Peer review Not commissioned; externally peer reviewed.