The association of toll-like receptor 4 gene polymorphisms with primary open angle glaucoma susceptibility: a meta-analysis

Chaiwiang, Narttaya; Poyomtip, Teera

doi:10.1042/bsr20190029

Cited by 7 publications

(5 citation statements)

References 58 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…When stratified by the subtype of glaucoma, our results demonstrated that TLR4 polymorphisms may have a tendency to influence the phenotypic features in POAG patients, instead of NTG patients, indicating that the pathogenesis and effect of TLR4 may be different between POAG and NTG. Chaiwiang and Poyomtip [36] conducted a similar meta-analysis recently and six allelic models were examined in their analysis. One notable difference was that their results indicated that only rs1927911 correlated with NTG in the homozygous model (GG vs. AA; OR=0.70; P=0.025), suggesting that individuals with the homozygous AA genotype exhibited increased risk of NTG when comparing with the GG homozygote.…”

Section: Discussionmentioning

confidence: 99%

Associations between TLR4 Polymorphisms and Open Angle Glaucoma: A Meta-Analysis

Lin

Huang

Sun

et al. 2019

BioMed Research International

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Associations between TLR4 Polymorphisms and Open Angle Glaucoma: A Meta-Analysis

Lin

Huang

Sun

et al. 2019

BioMed Research International

View full text Add to dashboard Cite

show abstract

Section: результати та їх обговоренняunclassified

“…Дослідження показали, що rs2149356G здатна утворювати мікроРНК, орієнтовану на гени аутофагії; існують асоціації між TLR4 rs1927911, rs12377632, rs2149356 та ПВКГ; rs4986790 A/G та rs4986791 C/T сильно знижують ризик ПВКГ [11]. Однак функції поліморфізмів TLR4 у моделі глаукоми повною мірою не визначені [11]. Як було показано вище, ПВКГ має зсув парадигми у бік запального захворювання та аутоімунітету, тому TLR4 відіграють роль у патогенезі глаукоми, яка класифікується як нейрозапальне та аутоімунне захворювання, та розглядаються як генетичний маркер ПВКГ, однак для підтримки цієї парадигми все ще потрібні додаткові докази [11].…”

Section: результати та їх обговоренняunclassified

“…Однак функції поліморфізмів TLR4 у моделі глаукоми повною мірою не визначені [11]. Як було показано вище, ПВКГ має зсув парадигми у бік запального захворювання та аутоімунітету, тому TLR4 відіграють роль у патогенезі глаукоми, яка класифікується як нейрозапальне та аутоімунне захворювання, та розглядаються як генетичний маркер ПВКГ, однак для підтримки цієї парадигми все ще потрібні додаткові докази [11].…”

Section: результати та їх обговоренняunclassified

See 1 more Smart Citation

PRIMARY OPEN ANGLE GLAUCOMA: MECHANISMS OF PATHOGENESIS AND GENETIC PREDISPOSITION. Review

Maidenko¹

2022

Med. Sci. of Ukr.

View full text Add to dashboard Cite

Relevance. Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with loss of retinal ganglion cells (RGCs) and narrowing of the visual fields in the eyes with a gonioscopic open angle. The main mechanisms of this are increased intraocular pressure (IOP), circulatory disorders, trabecular meshwork (TM), ischemic metabolic disorders and chronic inflammation. However, questions about the role of POAG genetic predisposition remain open. Objective: analysis of current data on the mechanisms of pathogenesis of progressive neuropathy in POAG and the role of genetic predisposition. Methods. The analysis of scientific publications in open international electronic scientometric databases: Scopus, PubMed, Web of Science, Google Scholar, SID, MagIran, IranMedex, IranDoc, ScienceDirect, Embase by keywords (a total of 67 sources). Search depth – 10 years (2012-2022). Results. There are more than 60 million glaucoma patients in the world, 20% of whom have an incurable stage. By 2040, the number of patients is projected to increase to 112 million, with POAG accounting for 75% of cases. Among the main mechanisms of glaucoma, an important role belongs to chronic inflammation and immune damage, which occur in response to ischemic injury. Prolonged inflammatory process leads to hypersecretion of inflammatory mediators and infiltration of inflammatory cells into ischemic tissue, which aggravates the effects of increased IOP and ischemia. It is known that mutations in the gene of Toll-like receptor 4 (TLR4) are associated with both infectious and non-infectious diseases, including POAG: activation of TLR4 initiates TM fibrosis, causes increased IOP, activates RGCs apoptosis in the model of acute glaucoma. TLR4 ligands, such as heat shock proteins and lipopolysaccharides are candidate antigens for glaucoma. TLR4 overexpression at retinal microglia and astrocytes induce an innate immune response through NF-κB activation, which enhances the expression of proinflammatory cytokines. Conclusions. A promising direction is to study the contribution of TLR4 mutations to the POAG mechanisms, which will identify the mechanisms of immune disorders and establish the genetic risk of individual mutations in different ethnic groups.

show abstract

“…Основным фактором риска развития глаукомы является повышенное внутриглазное давление (ВГД). Однако это не объясняет, по какой причине у пациентов развивается глаукома, в то время как их ВГД находится в норме [5]. В связи с этим в последнее время глаукому изучают с точки зрения иммунопатогенеза.…”

Section: Introductionunclassified

Association between polymorphic <i>eNOS</i> gene markers and risk of primary open-angle glaucoma in the Perm Region population

Гаврилова¹,

Kinkulkina

Avagyan

et al. 2022

Russian Journal of Immunology

View full text Add to dashboard Cite

Glaucoma is widely known to have a progressive course and occupy a leading place among the causes of vision loss and blindness. Increased intraocular pressure is the key harmful factor among the causes of glaucoma occurrence. In some cases, however, the progressive disease is also observed at normal values of ophthalmic tonus. Early diagnosis of glaucoma will allow for timely therapy, which in turn will reduce the risk of complications and prevent neuroopticopathy progression. According to the literature data, the pathogenesis of primary open-angle glaucoma is associated with nitric oxide (NO), due to imbalance between endothelium-produced vasoconstrictors and vasodilators, especially, endotelin-1 and nitric oxide. Decreased NO level combined with endotelin-1 hyperproduction is associated with development and progression of a number of ocular disorders including glaucomatous atrophy of the optic nerve. Since nitric oxide is produced by endothelial NO-synthase (eNOS), one may assume that eNOS is involved in pathogenesis of neurodegenerative changes in primary open-angle glaucoma. However, despite numerous studies on the pathogenesis of glaucoma, the distinct factors of innate immune response remain poorly studied. The purpose of the present study was a search for association between polymorphic markers (C774T, T786C, Glu298Asp) of the eNOS gene and the risk of primary open-angle glaucoma among the Perm Region residents. Peripheral blood of patients with primary open-angle glaucoma (the main group) and cataract without glaucoma (a comparison group) was used as initial biomaterial. In comparison group, arterial hypertension was most often encountered as concomitant pathology. Genomic DNA was first isolated from the blood samples, followed by rt-PCR using reagent kits for determining C774T, T786C, Glu298Asp polymorphic markers in the eNOS gene. The prevalence of polymorphic variants of the innate immunity genes T786C, C774T and Glu298Asp of the eNOS gene was analyzed in patients with primary open-angle glaucoma. There were no significant differences in the distribution of genotypes and alleles of eNOS gene for the C774T and Glu298Asp polymorphic markers. An increased frequency of homozygous TT genotype was found, along with decreased occurrence of C allele at the polymorphic T786C locus of the eNOS gene, as well as a trend for decreased frequency of the TC and CC genotypes. Arterial hypertension potentiated the negative effect of increased intraocular pressure upon the glaucoma-associated optic neuropathy. Conclusions. The studied changes in genotypes and allelic frequencies of eNOS gene may be regarded as risk factors that increase probability of the primary open-angle glaucoma and predict severity of the disease.

show abstract

The association of toll-like receptor 4 gene polymorphisms with primary open angle glaucoma susceptibility: a meta-analysis

Cited by 7 publications

References 58 publications

Associations between TLR4 Polymorphisms and Open Angle Glaucoma: A Meta-Analysis

Associations between TLR4 Polymorphisms and Open Angle Glaucoma: A Meta-Analysis

PRIMARY OPEN ANGLE GLAUCOMA: MECHANISMS OF PATHOGENESIS AND GENETIC PREDISPOSITION. Review

Association between polymorphic <i>eNOS</i> gene markers and risk of primary open-angle glaucoma in the Perm Region population

Contact Info

Product

Resources

About