Faculty of Optometry, Ramkhamhaeng University, Bangkok 10240, Thailand.
Faculty of Optometry, Ramkhamhaeng University, Bangkok 10240, Thailand
Biosci Rep. 2019 Apr 2;39(4). doi: 10.1042/BSR20190029. Print 2019 Apr 30.
Primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) cause irreversible blindness while current medications cannot completely inhibit disease progression. An understanding of immunopathogenesis is thus a keystone to develop novel drug targets and genetic markers are still required for early diagnosis. Toll-like receptor 4 (TLR4) is an essential player in inflammation in various diseases. However, the TLR4 polymorphisms have not been completely elucidated in both types of glaucoma. The aim of the present study was to identify the association between TLR4 polymorphism and glaucoma (POAG and NTG) via the use of a comprehensive review and meta-analysis. The relevant studies were collected from PubMed, Excerpta Medica Database (EMBASE), and Web of Science to identify eight included articles, assessed for quality by a modified Newcastle-Ottawa Scale (NOS) for gene association study. A meta-analysis was applied to calculate the pooled odds-ratio and 95% confidence intervals (CIs) to evaluate the association between TLR4 polymorphism and glaucoma. The results revealed that TLR4 rs1927911 A/G, rs12377632 C/T, and rs2149356 G/T significantly decrease the risk of POAG and NTG in allele contrast models 0.71-, 0.71-, and 0.67-fold, respectively. Moreover, rs4986790 A/G and rs4986791 C/T showed a stringent association with POAG in allele contrast, heterozygous, recessive, and overdominant models. In conclusion, this meta-analysis represented a significant correlation between TLR4 polymorphisms and both types of glaucoma suggesting that TLR4 might be involved in the pathogenesis of glaucoma and may be applied as a genetic marker for disease screening.
原发性开角型青光眼(POAG)和正常眼压型青光眼(NTG)可导致不可逆转的失明,而目前的药物治疗并不能完全抑制疾病进展。因此,了解免疫发病机制是开发新药物靶点的关键,并且仍然需要遗传标记物进行早期诊断。Toll 样受体 4(TLR4)是各种疾病中炎症的重要参与者。然而,TLR4 多态性在这两种类型的青光眼患者中尚未完全阐明。本研究的目的是通过综合回顾和荟萃分析,确定 TLR4 多态性与青光眼(POAG 和 NTG)之间的关联。从 PubMed、Excerpta Medica Database(EMBASE)和 Web of Science 中收集相关研究,使用改良的纽卡斯尔-渥太华量表(NOS)对基因关联研究进行质量评估。应用荟萃分析计算合并优势比和 95%置信区间(CI),以评估 TLR4 多态性与青光眼之间的关联。结果表明,TLR4 rs1927911 A/G、rs12377632 C/T 和 rs2149356 G/T 等位基因对比模型中,POAG 和 NTG 的风险分别降低了 0.71、0.71 和 0.67 倍。此外,rs4986790 A/G 和 rs4986791 C/T 在等位基因对比、杂合子、隐性和超显性模型中与 POAG 具有严格的关联。总之,这项荟萃分析表明 TLR4 多态性与两种类型的青光眼之间存在显著相关性,提示 TLR4 可能参与了青光眼的发病机制,并可作为疾病筛查的遗传标记物。