We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients.
Meta-analysis by autoimmune disease type revealed an association between both systemic lupus erythematosus and systemic sclerosis and the BANK1rs10516487 T allele (OR = 1.294, 95% CI = 1.232-1.360, p<1.0 × 10-8, heterogeneity p = 0.556; OR = 1.102, 95% CI = 1.027-1.183, p = 0.017, heterogeneity p = 0.048).
Taken together, our results suggest that the SLE susceptibility variants in the BANK1 gene may contribute to lupus by altering B cell signaling, increasing FOXO1 levels, and enhancing memory B cell development.
Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe.
Epistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe.
Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signalling and strengthens the role of IRF5 in disease susceptibility in a Northern European population.
SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti-dsDNA + SLE and were not associated with anti-dsDNA - SLE.
We selected and identified three SNPs of BANK1 associated with SLE (rs17266594, P = 1.949e-10; OR = 1.380; 95% CI: 1.250-1.525; rs10516487, P = 2.642e-13; OR = 1.317; 95% CI: 1.223-1.417; rs3733197, P = 3.452e-06; OR = 1.193; 95% CI: 1.107-1.286); one SNP of TNFAIP3 associated with SLE (rs2230926, P = 1.502e-12; OR = 1.826; 95% CI: 1.545-2.157).
Identification of BANK1 polymorphisms by unlabelled probe high resolution melting: association with systemic lupus erythematosus susceptibility and autoantibody production in Han Chinese.
With these studies, it has been established that a number of genes associated with SLE in Caucasians are also risk factors in Asians: HLA class II genes, STAT4, BANK1, BLK, IRF5, TNFSF4, ITGAM, etc., while there are also novel genetic risk factors identified by these studies in Asians, for instance, the ETS1 and WDFY4 in Chinese.
The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value=1.97 x 10(-5), odds ratio (OR)=1.22, 95% CI 1.12-1.34) and rs10516487 (corrected P-value=2.59 x 10(-5), OR=1.22, 95% CI 1.11-1.34).
Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 x 10(-3)).
To investigate 1 functional (rs17266594) and 2 potentially functional (rs10516487 and rs3733197) BANK1 variants, which were previously identified as systemic lupus erythematosus (SLE) susceptibility markers, to test whether they are associated with rheumatoid arthritis (RA).