Bcl-2 antagonist killer 1 (BAK1) polymorphisms influence the risk of developing autoimmune rheumatic diseases in women.
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.
Delgado-Vega
A M
AM
Center for Autoimmune Diseases Research, Rosario University, Bogotá, Colombia.
Castiblanco
J
J
Gómez
L M
LM
Diaz-Gallo
L-M
LM
Rojas-Villarraga
A
A
Anaya
J-M
JM
D001172:Arthritis, Rheumatoid / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D003105:Colombia; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012216:Rheumatic Diseases / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000235:genetics; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics*
C494772:BAK1 protein, human; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D050998:bcl-2 Homologous Antagonist-Killer Protein