机构：[1]The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P R China.重庆医科大学附属第一医院[2]Beijing Tongren Eye Center, Beijing Key Laboratory of Ophthalmology and Visual Science, Beijing Tongren Hospital, Capital Medical University, Beijing, P R China.首都医科大学附属北京同仁医院首都医科大学附属同仁医院[3]University Eye Clinic Maastricht, Maastricht, The Netherlands.
Several modulatory factors in the TLR signaling pathway including IRF3, IRF7, IRF8, TRIM20, MYD88 and NF-kappa B1 have been associated with autoimmune disease. In this study, we investigated the association of 13 SNPs for these genes with Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Haplotype and linkage disequilibrium (LD) analysis were performed by Haploview4.2. IRF8 mRNA expression and cytokine production was tested by real-time PCR and ELISA. Two SNPs near IRF8 were associated with BD (for rs17445836 GG genotype, Pc = 9.56 x 10(-8), OR = 2.044; for rs11642873 AA genotype, Pc = 9.24 x 10(-7), OR = 1.776). No significant association was found for the 13 SNPs tested with VKH syndrome. Haplotype analysis of the two positive SNPs revealed that the AG haplotype was significantly increased in BD patients (Pc = 2.60 x 10(-8), OR = 1.646). Functional studies revealed an increased mRNA expression of IRF8 and IFN-gamma production and a decreased production of IL-10 in rs17445836 carriers with the GG genotype. Increased expression of IRF8 as well as IFN-gamma production and a decreased production of IL-10 were found in individuals carrying the rs11642873/AA genotype. In conclusion, this study indicates that IRF8 may contribute to the genetic susceptibility of BD by regulating IRF8 expression and cytokine production.
基金：
This work was supported by Natural Science Foundation Major International (Regional) Joint Research Project
(81320108009), National Basic Research Program of China (973 Program) (2011CB510200), Key Project of
Natural Science Foundation(81130019),National Natural Science Foundation Project (31370893, 81200678),
Basic Research program of Chongqing (cstc2013jcyjC10001), Fundamental and Advanced Research Program
of Chongqing (cstc2015jcyjA10022), Science and Technology Project of Chongqing Municipal Education
Commission (KJ1500236), Scientific Research Program of Science and Technology Commission of Yuzhong
District of Chongqing (20150102), Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003),
National Key Clinical Specialties Construction Program of China, Key Project of Health Bureau of
Chongqing (2012-1-003), Research fund for Traditional Chinese Medicine of Chongqing Health and Family Planning Commission (ZY201401013), Chongqing Science & Technology Platform and Base Construction
Program(cstc2014pt-sy10002)and Fund for PAR-EU Scholars Program. Thanks to all donors enrolled in the
present study.
第一作者机构：[1]The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P R China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Jiang Yanni,Wang Hong,Yu Hongsong,et al.Two Genetic Variations in the IRF8 region are associated with Behcet's disease in Han Chinese[J].SCIENTIFIC REPORTS.2016,6:doi:10.1038/srep19651.
APA：
Jiang, Yanni,Wang, Hong,Yu, Hongsong,Li, Lin,Xu, Dengfeng...&Yang, Peizeng.(2016).Two Genetic Variations in the IRF8 region are associated with Behcet's disease in Han Chinese.SCIENTIFIC REPORTS,6,
MLA：
Jiang, Yanni,et al."Two Genetic Variations in the IRF8 region are associated with Behcet's disease in Han Chinese".SCIENTIFIC REPORTS 6.(2016)
