Comprehensive analysis of the association between UBAC2 polymorphisms and Behçet's disease in a Japanese population.

Behçet's disease (BD) is reportedly associated with polymorphisms of the ubiquitin-associated domain containing 2 (UBAC2) gene in Turkish, Italian, and Chinese populations. Here we investigated whether UBAC2 polymorphisms were associated with BD in a Japanese population. Using data from 611 Japanese BD patients and 737 Japanese controls who participated in our previous genome-wide association study, we analyzed the 58 genotyped single-nucleotide polymorphisms (SNPs) in the region 100 kb upstream and downstream of UBAC2. We also performed imputation analysis in the region, with 562 imputed SNPs included in the statistical analyses. Association testing revealed that the T allele of rs9517723 in the lncRNA LOC107984558 was significantly associated with ocular and central nervous system (CNS) lesions and showed the strongest association under the recessive model (TT vs. CT+CC: ocular lesion, Pc = 0.0099, OR = 1.56; CNS lesion, Pc = 0.0052, OR = 3.42). Expression analysis revealed that rs9517723 TT homozygotes showed significantly increased UBAC2 expression (P < 0.05). Our findings suggest that enhanced UBAC2 expression associated with the homozygous risk allele (TT) of rs9517723 could induce overactivation of ubiquitination-related pathway, resulting in the development of ocular and CNS lesions in BD.