FAS Gene Copy Numbers are Associated with Susceptibility to Behcet Disease and VKH Syndrome in Han Chinese

Previous studies have identified that disturbed apoptosis was involved in the pathogenesis of Behcet 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((R)) 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 x 10(-3)) and VKH syndrome (P = 2.56 x 10(-3)). Replication and combined study confirmed the association of high copy number (>2) of FAS with BD (P = 3.35 x 10(-8)) and VKH syndrome (P = 9.77 x 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.