title: Association of the C2-CFB locus with non-infectious uveitis, specifically predisposed to Vogt-Koyanagi-Harada disease.
abstract: Complement component 2 (C2) and factor B (CFB) are regulators of complement system and involved in the alternative pathway, which have been identified to be associated with multiple immune-related diseases. This study aimed to investigate the association of these genes with non-infectious intermediate and posterior uveitis. A total of 260 Chinese non-infectious uveitis patients were recruited, including 97 patients with Vogt-Koyanagi-Harada disease (VKH), 70 patients with intermediate uveitis (IU) and 93 patients with Behçet's disease (BD). Two hundred and ninety-three normal control subjects were also recruited. Five SNPs across the C2/CFB region were selected and genotyped using TaqMan SNP Genotyping Assays. Association analysis was adjusted for gender and stratified by different subtypes. The CFB SNP rs1048709 was significantly associated with non-infectious uveitis [P corr = 0.01, OR 1.49 (allele model) and P corr = 0.04, OR 1.58 (dominant model), respectively], and similar association was also detected between rs1048709 and female uveitis patients (P corr = 0.01, OR 1.70 and P corr = 0.049, OR 184, respectively). Moreover, subgroup analyses showed that CFB-rs1048709 was specifically associated with VKH, where significantly higher frequencies of A allele and AA homozygosity were observed in VKH patients compared with controls (P corr = 0.025 and P corr = 0.035, respectively), whereas none of these five SNPs was associated with IU or BD. In addition, a haplotype block across CFB (GTG) was significantly predisposed to uveitis with protective effect (OR 0.66, P corr = 0.048). Our results revealed a significant association of CFB with non-infectious uveitis, particularly predisposed to VKH disease. Genetic differences for uveitis could be gender-specific.
authors.affiliation: Eye Hospital, First Affiliated Hospital of Harbin Medical University, 23 Post Road, Nangang Region, Harbin, 150001, Heilongjiang, China.|The Centre for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.|Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Eye Hospital, First Affiliated Hospital of Harbin Medical University, 23 Post Road, Nangang Region, Harbin, 150001, Heilongjiang, China.
authors.forename: Jiao-jie
authors.initials: JJ
authors.lastname: Fan
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Eye Hospital, First Affiliated Hospital of Harbin Medical University, 23 Post Road, Nangang Region, Harbin, 150001, Heilongjiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Eye Hospital, First Affiliated Hospital of Harbin Medical University, 23 Post Road, Nangang Region, Harbin, 150001, Heilongjiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Eye Hospital, First Affiliated Hospital of Harbin Medical University, 23 Post Road, Nangang Region, Harbin, 150001, Heilongjiang, China. liuping_53@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001528:Behcet Syndrome / Q000175:diagnosis / Q000235:genetics; D003175:Complement C2 / Q000235:genetics*; D011415:Complement Factor B / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014605:Uveitis / Q000175:diagnosis / Q000235:genetics; D014607:Uveomeningoencephalitic Syndrome / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
chemical_list: D003175:Complement C2; D011415:Complement Factor B
keywords: C2; CFB; Complement system; Uveitis