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.
Highlights
The T cell ubiquitin ligand proteins (TULA) family is characterized by function as suppressors of T cell receptor signalling
Recent studies have showed that single nucleotide polymorphisms (SNPs) of the UBASH3a gene are associated with some autoimmune diseases, like type 1 diabetes (T1D), celiac disease (CD), rheumatoid arthritis (RA) and vitiligo, suggesting that this gene could play an important role in the pathogenesis of autoimmune disorders [3,4,5,6,7,8]
UBASH3a is implicated in the regulation of tyrosine phosphorylation levels within T cells and is involved in facilitates the apoptosis induced in these cells
Summary
The T cell ubiquitin ligand proteins (TULA) family is characterized by function as suppressors of T cell receptor signalling. One of the members of the TULA family proteins is the ubiquitin associated and Src-homology 3 (SH3) domain containing A (UBASH3a) which is expressed only in lymphoid cells and facilitates apoptosis induced in T cells by certain stimuli, such as growth factor withdrawal [1]. The lack of TULA proteins resulted in hyper-reactivity of T cells [1] Evidence for both B and T lymphocyte hyper-reactivity is typically observed in autoimmune disorders [2]. These disorders are characterized by an inappropriate, excessive, inflammatory response against self, resulting in tissue destruction. Recent studies have showed that single nucleotide polymorphisms (SNPs) of the UBASH3a gene are associated with some autoimmune diseases, like type 1 diabetes (T1D), celiac disease (CD), rheumatoid arthritis (RA) and vitiligo, suggesting that this gene could play an important role in the pathogenesis of autoimmune disorders [3,4,5,6,7,8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
