title: Evidence of new risk genetic factor to systemic lupus erythematosus: the UBASH3A gene.
abstract: The ubiquitin associated and Src-homology 3 (SH3) domain containing A (UBASH3a) is a suppressor of T-cell receptor signaling, underscoring antigen presentation to T-cells as a critical shared mechanism of diseases pathogenesis. The aim of the present study was to determine whether the UBASH3a gene influence the susceptibility to systemic lupus erythematosus (SLE) in Caucasian populations. We evaluated five UBASH3a polymorphisms (rs2277798, rs2277800, rs9976767, rs13048049 and rs17114930), using TaqMan® allelic discrimination assays, in a discovery cohort that included 906 SLE patients and 1165 healthy controls from Spain. The SNPs that exhibit statistical significance difference were evaluated in a German replication cohort of 360 SLE patients and 379 healthy controls. The case-control analysis in the Spanish population showed a significant association between the rs9976767 and SLE (Pc = 9.9E-03 OR = 1.21 95%CI = 1.07-1.37) and a trend of association for the rs2277798 analysis (P = 0.09 OR = 0.9 95%CI = 0.79-1.02). The replication in a German cohort and the meta-analysis confirmed that the rs9976767 (Pc = 0.02; Pc = 2.4E-04, for German cohort and meta-analysis, respectively) and rs2277798 (Pc = 0.013; Pc = 4.7E-03, for German cohort and meta-analysis, respectively) UBASH3a variants are susceptibility factors for SLE. Finally, a conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs9976767 polymorphism. Our results suggest that UBASH3a gene plays a role in the susceptibility to SLE. Moreover, our study indicates that UBASH3a can be considered as a common genetic factor in autoimmune diseases.
authors.affiliation: Cellular Biology and Immunology Department, Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas (IPBLN- Consejo Superior de Investigaciones Científicas), Granada, Spain. lina.diaz@ipb.csic.es
authors.forename: Lina-Marcela
authors.initials: LM
authors.lastname: Diaz-Gallo
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.forename: Jose Mario
authors.initials: JM
authors.lastname: Sabio
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: García-Hernández
authors.forename: Enrique
authors.initials: E
authors.lastname: de Ramón
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.lastname: Torsten Witte
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
authors.forename: María F
authors.initials: MF
authors.lastname: González-Escribano
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C423262:UBASH3A protein, human
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