Abstract
Background Previous studies exploring the association between toll-like receptor 4 (TLR4) polymorphisms and open angle glaucoma (OAG) presented inconsistent results. We aimed to investigate the association between TLR4 polymorphisms and OAG. Methods A systematic literature search was conducted in PubMed, EMBASE, ISI Web of Knowledge, and the Cochrane Library up to 31 December 2018. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated, followed by stratification analyses according to ethnicity and glaucoma subtype. Results TLR4 rs7037117 polymorphism had significant associations with increased risk of OAG in allelic model (OR=1.25; 95%CI: 1.09-1.44; P=0.002) and recessive model (OR=1.49; 95%CI: 1.08-2.04; P=0.01). With regard to rs10759930, rs12377632, and rs2149356, the results showed significant increased risks in all genetic models (all P<0.05), whereas, for rs1927914, rs11536889, and rs7045953, no significant associations were identified in any genetic model (all P>0.05). Furthermore, the association of rs1927911 with OAG risk was found to be significant in recessive model (OR=1.34; 95%CI: 1.06-1.71; P=0.02). As for rs4986790 and rs4986791, meta-analyses were not performed due to the limited number of studies and the ethnic differences. Subgroup analysis indicated that the above polymorphisms with significant differences might increase the susceptibility in POAG patients. As for the ethnicity, rs7037117, rs10759930, and rs1927911 might increase the risk in Asians, while rs12377632 and rs2149356 might increase the risk in Asians and Mexicans. Conclusion The meta-analysis highlighted that certain mutations of some TLR4 polymorphisms might increase the susceptibility of OAG. However, TLR4 polymorphisms are still far from being candidate genetic biomarkers for OAG. Additional researches involving larger scale epidemiological studies are warranted to validate our results.
Highlights
Glaucoma is a group of neurodegenerative diseases that can lead to irreversible blindness
Open angle glaucoma (OAG) is the most common form, accounting for about 85% of glaucoma cases. It is characterized by progressive degeneration of retinal ganglion cells (RGCs) and subsequent irrevocable vision loss, which can occur with either elevated intraocular pressure (IOP) or normal IOP, commonly termed as primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG), respectively
Combined data revealed that toll-like receptor 4 (TLR4) rs7037117 polymorphism had significant associations with increased risk of open angle glaucoma (OAG) in allelic model (OR=1.25; 95% confidence interval (95%confidence interval (CI)): 1.09-1.44; P=0.002) and recessive model (OR=1.49; 95%CI: 1.08-2.04; P=0.01) (Figure 3)
Summary
Glaucoma is a group of neurodegenerative diseases that can lead to irreversible blindness. Previous studies exploring the association between toll-like receptor 4 (TLR4) polymorphisms and open angle glaucoma (OAG) presented inconsistent results. TLR4 rs7037117 polymorphism had significant associations with increased risk of OAG in allelic model (OR=1.25; 95%CI: 1.09-1.44; P=0.002) and recessive model (OR=1.49; 95%CI: 1.08-2.04; P=0.01). With regard to rs10759930, rs12377632, and rs2149356, the results showed significant increased risks in all genetic models (all P0.05). The association of rs1927911 with OAG risk was found to be significant in recessive model (OR=1.34; 95%CI: 1.06-1.71; P=0.02). Subgroup analysis indicated that the above polymorphisms with significant differences might increase the susceptibility in POAG patients. The meta-analysis highlighted that certain mutations of some TLR4 polymorphisms might increase the susceptibility of OAG. Additional researches involving larger scale epidemiological studies are warranted to validate our results
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