The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China.
Invest Ophthalmol Vis Sci. 2013 Dec 30;54(13):8384-92. doi: 10.1167/iovs.13-12878.
TLR2, TLR4, TLR8, and TLR9 have been reported to be associated with several autoimmune diseases. The current study aimed to explore whether singe nucleotide polymorphisms (SNPs) of these four genes were associated with ocular Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU) with or without ankylosing spondylitis (AS), or pediatric uveitis in Han Chinese.
Genotyping was performed by PCR-restriction fragment length polymorphism. The first stage study comprised 400 ocular BD patients, 400 VKH syndrome patients, 400 AAU ± AS patients, 400 pediatric uveitis patients and 600 healthy subjects. The second stage included 438 ocular BD patients and 1000 healthy subjects. Allele and genotype frequencies were compared between patients and controls using the χ(2) test. Real-time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls. Levels of TNF-α, IL-6, IL-10, and IL-1beta in culture supernatants were measured by ELISA.
In the first stage study, only the frequencies of the rs2289318/TLR2 genotype A and C allele and rs3804099/TLR2 genotype CT were significantly higher in ocular BD patients (Pc = 0.048; Pc = 0.008; Pc = 0.005, respectively) compared with controls. The second stage and combined studies confirmed the association (Pc = 0.001; Pc = 6.89E-06, Pc = 2.426E-06, respectively). TLR2 mRNA expression in PBMCs was increased in healthy carriers of the CC genotype of rs2289318/TLR2 and TT genotype of rs3804099/TLR2 following stimulation with peptidoglycan (PGN; P = 0.028; P = 0.004, respectively). No effect of the various TLR2 rs2289318 and rs3804099 genotypes on the release of TNF-α, IL-6, IL-10, and IL-1beta could be detected.
This study provides evidence that the TLR2 gene is involved in the susceptibility to ocular BD.
TLR2、TLR4、TLR8 和 TLR9 已被报道与多种自身免疫性疾病相关。本研究旨在探讨这些基因的单核苷酸多态性（SNP）是否与汉族人群的眼型 Behçet 病（BD）、Vogt-小柳-原田综合征（VKH）、伴有或不伴有强直性脊柱炎（AS）的急性前葡萄膜炎（AAU）或儿童葡萄膜炎相关。
采用 PCR-限制性片段长度多态性方法进行基因分型。第一阶段研究包括 400 例眼型 BD 患者、400 例 VKH 综合征患者、400 例 AAU±AS 患者、400 例儿童葡萄膜炎患者和 600 例健康对照者。第二阶段包括 438 例眼型 BD 患者和 1000 例健康对照者。采用 χ2检验比较患者和对照组之间的等位基因和基因型频率。采用实时 PCR 检测来自健康对照者外周血单个核细胞的 mRNA 表达。通过 ELISA 测定培养上清液中 TNF-α、IL-6、IL-10 和 IL-1β的水平。
在第一阶段研究中，与对照组相比，眼型 BD 患者 TLR2 基因 rs2289318/TLR2 基因型 A 和 C 等位基因以及 rs3804099/TLR2 基因型 CT 的频率显著升高（Pc=0.048；Pc=0.008；Pc=0.005）。第二阶段和联合研究证实了这种相关性（Pc=0.001；Pc=6.89E-06，Pc=2.426E-06）。在肽聚糖（PGN）刺激后，TLR2 基因 rs2289318/TLR2 的 CC 基因型和 rs3804099/TLR2 的 TT 基因型的健康携带者的 PBMCs 中 TLR2 mRNA 表达增加（P=0.028；P=0.004）。未检测到 TLR2 基因 rs2289318 和 rs3804099 各种基因型对 TNF-α、IL-6、IL-10 和 IL-1β释放的影响。
本研究提供了证据表明 TLR2 基因参与了眼型 BD 的易感性。
