title: Comprehensive analysis of the association between UBAC2 polymorphisms and Behçet's disease in a Japanese population.
abstract: 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.
authors.affiliation: Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yamazoe
authors.affiliation: Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan. akmeguro@yokohama-cu.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Meguro
authors.affiliation: Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan.|Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Shibuya
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, 236-0004, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Mizuki
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001528:Behcet Syndrome / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics*
chemical_list: C470301:UBA2 protein, human; D044764:Ubiquitin-Activating Enzymes