Association of TLR2 Gene Polymorphisms With Ocular Behcet's Disease in a Chinese Han Population
Association of TLR2 Gene Polymorphisms With Ocular Behcet's Disease in a Chinese Han Population
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DOI：
10.1167/iovs.13-12878
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发表时间：
2013-12-01
影响因子：
4.4
通讯作者：
Yang, Peizeng
中科院分区：
文献类型：
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作者：
Fang, Jing;Hu, Ranran;Yang, Peizeng
目的。据报道，TLR2、TLR4、TLR8和TLR9与几种自身免疫性疾病有关。本研究旨在探讨这四种基因的单核苷酸多态性（snp）是否与汉族眼部白塞病（BD）、Vogt-Koyanagi-Harada （VKH）综合征、急性前葡萄膜炎（AAU）伴或不伴强直性脊柱炎（AS）或儿童葡萄膜炎相关。采用聚合酶链反应-限制性片段长度多态性进行基因分型。第一阶段研究包括400例眼部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名健康受试者。第二阶段纳入438名眼性双相障碍患者和1000名健康受试者。采用chi(2)检验比较患者和对照组的等位基因和基因型频率。Real-time PCR检测健康对照外周血细胞mRNA表达情况。elisa法检测培养上清中tnf - α、IL-6、IL-10、il -1 β的水平。在一期研究中，眼部BD患者中只有rs2289318/TLR2基因型A和C等位基因以及rs3804099/TLR2基因型CT的频率显著高于对照组（P-c = 0.048; P-c = 0.008; P-c = 0.005）。第二阶段和联合研究证实了这种相关性（P-c = 0.001; P-c = 6.89E-06, P-c = 2.426E-06）。健康rs2289318/TLR2 CC基因型携带者和rs3804099/TLR2 TT基因型携带者经肽聚糖刺激后，PBMCs中TLR2 mRNA表达增加（PGN; P = 0.028; P = 0.004）。不同TLR2 rs2289318和rs3804099基因型未检测到对tnf - α、IL-6、IL-10和il -1 β释放的影响。本研究提供了TLR2基因参与眼部双相障碍易感性的证据。
PURPOSE. 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 Behcet's disease (BD), Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU) with or without ankylosing spondylitis (AS), or pediatric uveitis in Han Chinese.METHODS. 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 chi(2) test. Real-time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls. Levels of TNF-alpha, IL-6, IL-10, and IL-1beta in culture supernatants were measured by ELISA.RESULTS. 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 (P-c = 0.048; P-c = 0.008; P-c = 0.005, respectively) compared with controls. The second stage and combined studies confirmed the association (P-c = 0.001; P-c = 6.89E-06, P-c = 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-alpha, IL-6, IL-10, and IL-1beta could be detected.CONCLUSIONS. This study provides evidence that the TLR2 gene is involved in the susceptibility to ocular BD.