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Hongsong Yu, Le Luo, Lili Wu, Aize Kijlstra, Peizeng Yang; FAS gene copy numbers are associated with susceptibility to Behçet’s disease and VKH syndrome in Han Chinese. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5992.
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© ARVO (1962-2015); The Authors (2016-present)
To determine whether copy number Variations (CNVs) of apoptosis-related genes, including FAS, caspase8, caspase3 and BCL-2, are associated with Behçet’s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.
CNVs of the target genes were quantified by TaqMan® Copy Number Assays and performed in 96-well plates on the Applied Biosystems 7500 Real-Time PCR System. A two-stage association study was performed in 1014 BD patients, 1051 VKH syndrome patients and 2076 healthy controls. The biological effect of CNVs was validated with mRNA expression assays.
In the first stage study, an association analysis of 4 CNVs was performed in 300 patients with BD, 300 patients with VKH syndrome and 600 controls. An increased frequency of high FAS gene copy number (>2) was found in BD (P=5.42×10-4, OR=2.22) and VKH syndrome (P=2.56×10-3, OR=2.03). No significant association between CNVs of the other three genes and BD or VKH syndrome was observed. In the second stage study, an association analysis of FAS gene CNVs was performed in 714 BD, 751 VKH syndrome patients and 1476 controls. The second stage and combined study confirmed the association of high copy number (>2) of the FAS gene with BD (P=9.52×10-11, OR=2.30) and VKH syndrome (P=9.77×10-8, OR=2.01). A significant up-regulated mRNA expression of the FAS gene was observed in anti-CD3/CD28 antibodies-stimulated CD4+ T cells from healthy individuals carrying a high gene copy number (>2) as compared to normal diploid 2 copy number (P=0.043) or low copy number (<2) (P=0.034) carriers. Moreover, the mRNA expression of FAS gene both in active patients with BD and VKH syndrome was significantly higher than that in healthy controls (P=0.035 and P=0.028, respectively).
Our findings suggest that a high copy number of FAS gene is associated with an increased risk of BD and VKH syndrome in Han Chinese, which is likely related to an increased expression of FAS in patients with BD and VKH syndrome.
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