Association of Toll-like receptor 4 gene polymorphisms with normal tension glaucoma
Association of Toll-like receptor 4 gene polymorphisms with normal tension glaucoma
复制标题
DOI：
10.1167/iovs.07-1575
复制
发表时间：
2008-10-01
影响因子：
4.4
通讯作者：
Mizuki, Nobuhisa
中科院分区：
文献类型：
--
作者：
Shibuya, Etsuko;Meguro, Akira;Mizuki, Nobuhisa
目的。Toll样受体4(TLR4)是一种跨膜受体，介导对外源性和内源性配体的免疫反应，并与热休克蛋白相互作用，据报道热休克蛋白与正常眼压性青光眼有关。本研究旨在探讨TLR4基因多态性是否与NTG相关。方法收集250例日本NTG患者和318例日本健康对照组。对TLR4基因的8个单核苷酸多态(SNPs)进行了基因分型，并分析了病例组和对照组之间的等位基因和表型多样性。结果：所有SNPs(D‘>；=0.85)之间存在很强的连锁不平衡，位于一个单倍型区块中。在等位基因多样性方面，3个SNPs(rs10759930、rs1927914和rs7037117)的次要等位基因携带明显增加的NTG风险。就基因多样性而言，携带6个SNPs(rs10759930、rs1927914、rs1927911、rs12377632、rs2149356和rs7037117)微小等位基因的个体患NTG的风险增加1.47-1.65倍。位于TLR4基因3‘端非翻译区的rs7037117与NTG的关联最强，当与rs10759930合并为单倍型时，关联最强(P=0.0038，P(C)=0.0095)。结论：TLR4基因的多个SNP与NTG的风险有关。提示TLR4信号网络中的配体和/或细胞因子可能是NTG发生发展的危险因素。
PURPOSE. Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands and interacts with heat shock proteins, which are reportedly involved in normal tension glaucoma (NTG). This study was undertaken to investigate whether TLR4 polymorphisms are associated with NTG.METHODS. Two hundred fifty Japanese patients with NTG and 318 Japanese healthy control subjects were recruited. Eight single-nucleotide polymorphisms (SNPs) in the TLR4 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects.RESULTS. Strong linkage disequilibrium was observed among all SNPs (D' >= 0.85), which were located in one haplotype block. With respect to allelic diversity, the minor allele of three SNPs (rs10759930, rs1927914, and rs7037117) carried a significantly increased risk of NTG. With regard to genotypic diversity, individuals with the minor allele of six SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, and rs7037117) had a 1.47- to 1.65-fold increased risk of NTG. rs7037117, located in the 3'-untranslated region of TLR4, was most strongly associated with NTG, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 0.0038, P(c) = 0.0095).CONCLUSIONS. Multiple SNPs in the TLR4 gene are associated with the risk of NTG. This finding suggests that the ligands and/or cytokines involved in the TLR4 signaling network may be risk factors for the development of NTG.