Zheng Minming, Yu Hongsong, Zhang Lijun, Li Hua, Liu Yunjia, Kijlstra Aize, Yang Peizeng
The First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China.
University Eye Clinic Maastricht, Maastricht, The Netherlands.
Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8280-7. doi: 10.1167/iovs.15-18035.
This study was conducted to explore the association of autophagy-related genes (ATGs) single nucleotide polymorphisms (SNPs) with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.
A two-stage association study was carried out in 940 BD, 1061 VKH, and 2007 healthy controls. Genotyping for genetic variants of 10 autophagy family genes (ATG5, ATG7, ATG10, ATG16L1, IRGM, LKKR2, ATG2A, DAP, ULK1, and TSC1) was performed using PCR-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP assays. Gene expression was quantified by real-time PCR.
In the cohort of BD patients, we observed that the TT genotype of rs573775/ATG5 decreased susceptibility to BD (Pc = 8.35 × 10-6, OR = 0.490). In the case of VKH patients, the AC genotype of rs4703863/ATG10 increased susceptibility to VKH syndrome (Pc = 9.94 × 10-5, OR = 1.444), whereas the A allele and AA genotype of rs4703863 (Pc = 7.06 × 10-5, OR = 0.745; Pc = 6.34 × 10-6, OR = 0.669, respectively) acted as protective factors for VKH. Functional experiments showed an increased ATG5 expression by LPS stimulated PBMCs in TT cases of rs573775 compared with controls. The level of ATG5 mRNA in active BD patients not receiving immunosuppression was significantly higher than that in healthy controls.
This study demonstrated an association of ATG5 rs573775 with BD and ATG10 rs4703863 with VKH syndrome in a Chinese Han population. Furthermore, a variant of the ATG5 gene was shown to be correlated with ATG5 expression.
本研究旨在探讨自噬相关基因（ATGs）单核苷酸多态性（SNPs）与中国汉族人群白塞病（BD）和伏格特-小柳-原田综合征（VKH）之间的关联。
对940例BD患者、1061例VKH患者和2007例健康对照进行两阶段关联研究。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）或TaqMan SNP分析法对10个自噬家族基因（ATG5、ATG7、ATG10、ATG16L1、IRGM、LKKR2、ATG2A、DAP、ULK1和TSC1）的基因变异进行基因分型。通过实时PCR定量基因表达。
在BD患者队列中，我们观察到rs573775/ATG5的TT基因型降低了患BD的易感性（Pc = 8.35×10 - 6，OR = 0.490）。对于VKH患者，rs4703863/ATG10的AC基因型增加了患VKH综合征的易感性（Pc = 9.94×10 - 5，OR = 1.444），而rs4703863的A等位基因和AA基因型（分别为Pc = 7.06×10 - 5，OR = 0.745；Pc = 6.34×10 - 6，OR = 0.669）对VKH起保护作用。功能实验表明，与对照组相比，rs573775的TT病例中脂多糖刺激的外周血单个核细胞（PBMCs）的ATG5表达增加。未接受免疫抑制的活动性BD患者的ATG5 mRNA水平显著高于健康对照。
本研究证明了中国汉族人群中ATG5 rs573775与BD以及ATG10 rs4703863与VKH综合征之间的关联。此外，ATG5基因的一个变异体与ATG5表达相关。
