Evidence of New Risk Genetic Factor to Systemic Lupus Erythematosus: The <i>UBASH3A</i> Gene

<div><p>The ubiquitin associated and Src-homology 3 (SH3) domain containing A (<i>UBASH3a</i>) 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 <i>UBASH3a</i> gene influence the susceptibility to systemic lupus erythematosus (SLE) in Caucasian populations. We evaluated five <i>UBASH3a</i> 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) <i>UBASH3a</i> 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 <i>UBASH3a</i> gene plays a role in the susceptibility to SLE. Moreover, our study indicates that <i>UBASH3a</i> can be considered as a common genetic factor in autoimmune diseases.</p>