AB0009 ASSOCIATION BETWEEN POLYMORPHISMS OF BANK1 AND MANIFESTATIONS OF SLE
Authors: D. D. González-Castillo, R. E. Barbosa-Cobos, G. E. Lugo Zamudio, M. A. Saavedra, R. E. Sánchez-Briones, I. Alemán-Ávila, J. Ramírez Bello
Journal: Annals of the Rheumatic Diseases (2020)

Background: BANK1 encodes an adapter/scaffold protein primarily expressed in B cells, which is involved in cell signaling and activation. Genome-wide association studies (GWAS) have identified different BANK1 single nucleotide variants (SNVs) associated with SLE primarily in European or Asian-derived populations. Interestingly, we recently have documented an association between this gene and susceptibility to systemic lupus erythematosus (SLE) in Mexican population. Objectives: To determine whether the BANK1 R61H (rs10516487G/A) and A383T (rs3733197G/A) SNVs are associated with clinical and immunological manifestations in SLE. Methods: Our study included 123 Mexican women with SLE (SLICC 2012 criteria). Genotyping of the two BANK1 SNVs were obtained by TaqMan probes and real-time PCR. An association study was performed between the alleles and genotypes of BANK1 R61H and A383T with the clinical and immunological manifestations included in the SLE SLICC classification criteria. Hardy-Weinberg equilibrium and an association study was performed using Finetti, a p value ≤ 0.05 indicated association. Results: We identify an average age of 38.5±12. Cases and controls remained in Hardy-Weinberg equilibrium. An association with susceptibility to SLE was found between genotypes of the two BANK1 SNVs and joint manifestations (rs1051487G/A; AA + GA vs GG, OR 4.45, p =0.004, rs3733197G/A; AA + GA vs GG, OR 2.66, p =0.032, respectively), as well as with protection for neurological and renal involvement (rs1051487G/A, OR 0.16, p =0.02, rs3733197G/A; OR 0.40, p =0.02, respectively) (Table 1a and b). No association was found with other clinical manifestations. Conclusion: Our data in the Mexican population show that both BANK1 R61H and A383T SNVs are risk factors for synovitis. On the other hand, these BANK1 R61H and A383T variants are protective factors for neurological and renal damage, respectively. References: [1]Ramírez-Bello J, Jiménez-Morales S, Montufar-Robles I, et al. BLK and BANK1 polymorphisms and interactions are associated in Mexican patients with systemic lupus erythematosus. Inflamm Res. 2019;68:705-13 [2]J. De Azevêdo Silva, C. Addobbati, P. Sandrin-Garcia and S. Crovella. Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations. Current Genomics. 2014;15:52-65 [3]Sánchez E, Rasmussen A, Riba L, Acevedo E, Kelly J, Langefeld CD, et al. Impact of Genetic Ancestry and Socio-Demographic Status on the Clinical Expression of Systemic Lupus Erythematosus in Amerindian-European Populations. Arthritis Rheum. 2012; 64(11):3687–3694 [4]Castillejo-López C, Delgado-Vega AM, Wojcik J, et al. Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK. Ann Rheum Dis. 2012;71:136–42 [5]Kozyrev SV, Abelson AK, Wojcik J, et al. Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nat Genet. 2008;40:211-6 Disclosure of Interests: None declared