Open AccessComprehensive analysis of the association between UBAC2 polymorphisms and Behçet’s disease in a Japanese population
Author(s) -
Kyoko Yamazoe,
Akira Meguro,
Masaki Takeuchi,
Etsuko Shibuya,
Shigeaki Ohno,
Nobuhisa Mizuki
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-00877-3
Subject(s) - behcet's disease , behcet disease , disease , population , medicine , genetics , biology , environmental health
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, P c = 0.0099, OR = 1.56; CNS lesion, P c = 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.