A Variant Of UBAC2 In Behçet’s Disease

Abstract

Purpose: : Behçet’s disease (BD) is a systemic disorder characterized by recurrent uveitis, oral ulceration, multiform skin lesions and genital ulceration. Autoimmunity and gene factors have been implicated in the pathogenesis of this disease. To identify genetic factors associated with the susceptibility to BD.

Methods: : We performed a meta-analysis based on two independent genome-wide association studies (GWAS). Subsequent validating investigation was carried out on a larger sample size. Real-time PCR and luciferase reporter assay were performed to test the function of the identified promoter polymorphism.

Results: : The GWAS result showed that ubiquitin-associated domain containing 2 (UBAC2) was associated with the susceptibility to BD both in Chinese and in Turkish populations. The fine-mapping association study of UBAC2 identified six novel risk SNPs for BD in Chinese cohort (overall P<9×10^-4), three of them were verified in validation study (P_c=0.003, OR=1.38; Pc=0.033, OR=1.30; Pc=0.0018, OR=1.43, respectively). Functional analysis showed that the risk T allele of the promoter polymorphism rs3825427 had a significantly lower promoter activity than the non-risk G allele (P=0.002) and a decreased expression of UBAC2 in the PBMCs and skin of normal controls carrying the risk T allele than that in individuals with the G allele (P=0.045, P=0.025; respectively).The mRNA expression of UBAC2 was significantly decreased in PBMCs and skin of BD patients as compared with controls (P=0.023; P=0.046, respectively).

Conclusions: : This study identifies a predisposition gene to Behçet’s disease, UBAC2, and suggests that UBAC2 may be involved in the development of BD through its transcriptional modulation.

Keywords: uveitis-clinical/animal model • genetics