title: FAS Gene Copy Numbers are Associated with Susceptibility to Behçet Disease and VKH Syndrome in Han Chinese.
abstract: Previous studies have identified that disturbed apoptosis was involved in the pathogenesis of Behçet disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome. This study aims to investigate whether copy number variations of apoptosis-related genes, including FAS, CASPASE8, CASPASE3, and BCL2, are associated with BD and VKH syndrome in Han Chinese. A two-stage association study was performed in 1,014 BD patients, 1,051 VKH syndrome patients, and 2,076 healthy controls. TaqMan(®) Copy Number Assays and real-time PCR were performed. The first-stage study showed that increased frequency of high FAS copy number (>2) was found in BD (P = 1.05 × 10(-3) ) and VKH syndrome (P = 2.56 × 10(-3) ). Replication and combined study confirmed the association of high copy number (>2) of FAS with BD (P = 3.35 × 10(-8) ) and VKH syndrome (P = 9.77 × 10(-8) ). A significant upregulated mRNA expression of FAS was observed in anti-CD3/CD28 antibodies-stimulated CD4(+) T cells from individuals carrying a high gene copy number (>2) as compared to normal diploid 2 copy number carriers (P = 0.004). Moreover, the mRNA expression of FAS both in active patients with BD and VKH syndrome was significantly higher than that in controls (P = 0.001 and P = 0.007, respectively). Our findings suggest that a high copy number of FAS gene confers risk for BD and VKH syndrome.
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Hongsong
authors.initials: H
authors.lastname: Yu
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Luo
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wu
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Minming
authors.initials: M
authors.lastname: Zheng
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Yunjia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Cao
authors.affiliation: University Eye Clinic Maastricht, Maastricht, The Netherlands.
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001528:Behcet Syndrome / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics; D053181:Caspase 8 / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D014607:Uveomeningoencephalitic Syndrome / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8
keywords: BD; Behcet disease; FAS; VKH syndrome; copy number variation