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An updated meta-analysis: apolipoprotein E genotypes and risk of primary open-angle glaucoma.

ABSTRACT: PURPOSE:To study the association of apolipoprotein E (APOE) polymorphisms and primary open-angle glaucoma (POAG). METHODS:After a systematic literature search, all relevant studies evaluating the association between APOE polymorphisms and POAG were included. All statistical tests were calculated with Stata 11.0. RESULTS:Twelve independent studies on the APOE gene (1,971 cases, 1,756 controls) and POAG were included. A significant association between the APOE gene and POAG was found in the genetic model of ?4/?4 versus ?3/?3 (odds ratio [OR] = 2.09, 95% confidence interval [CI] = 1.12-3.88, p = 0.02). However, no association was detected in the models of ?2/?2 versus ?3/?3, ?2/?3 versus ?3/?3, ?2/?4 versus ?3/?3, ?3/?4 versus ?3/?3, allele ?2 versus allele ?3, and allele ?4 versus allele ?3. Subgroup analyses showed that a statistically significant association between the APOE gene and the risk of POAG existed in the genetic model of ?4/?4 versus ?3/?3 in Asians (OR = 3.55, 95% CI = 1.06-11.87, p = 0.04). No association was identified between the APOE gene and the risk of POAG in Caucasians. CONCLUSIONS:The present meta-analysis indicated that the ?4/?4 genotype is associated with increased risk of POAG in Asians.

SUBMITTER: Liao R

PROVIDER: S-EPMC4105115 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Blindness in glaucoma: primary open-angle glaucoma versus primary angle-closure glaucoma-a meta-analysis.

Project description:AimTo estimate the risk of blindness with primary angle-closure glaucoma (PACG) compared to primary open-angle glaucoma (POAG) in those population-based studies that reported blindness rates for both PACG and POAG.MethodA systematic search was performed in PubMed for articles published in English between 2000 and 2020 reporting the prevalence of POAG as well as PACG among various ethnic populations. A study was included if it was (1) population-based (2) had published prevalence and blindness rates for both PACG and POAG in the same cohort. (3) Glaucoma was defined as per the International Society for Geographical and Epidemiological Ophthalmology (ISGEO) criteria. The proportion of blindness for both POAG and PACG for each study and the cumulative proportion taking all the studies were calculated.ResultsWe included 23 studies with 78,434 participants. POAG was diagnosed in 1702 persons with 151 (8.9%) blind. There were 724 cases of PACG with 196 (27.0%) blind. The risk ratio of blindness in PACG to POAG varied from 0.73 to 10.6 among the studies. The cumulative risk ratio was 2.39 (95% confidence interval (CI); 1.99, 2.87). Risk ratios for studies including visual field restriction while defining blindness were similar to studies that did not (1.92 vs 2.64, P = 0.11). Risk ratios were also similar for studies that used greater than 2 instead of 3 or more quadrants of iridotrabecular contact to define angle closure (2.79 vs 2.25).ConclusionPrimary angle-closure disease is more likely to be associated with blindness.

| S-EPMC9582001 | biostudies-literature

Apolipoprotein E gene ?4?4 is associated with elevated risk of primary open angle glaucoma in Asians: a meta-analysis.

Project description:BACKGROUND: Epidemiological studies have evaluated the association between Apolipoprotein E (APOE) gene ?2/?3/?4 polymorphism and glaucoma susceptibility. However, the published data are still inconclusive. The aim of the present study is to evaluate the impact of APOE gene ?2/?3/?4 polymorphism on glaucoma risk by using meta-analysis. METHODS: A comprehensive literature search of PubMed, EMBASE, Cochrane, Elsevier Science Direct and CNKI databases was conducted to identify relevant articles, with the last report up to January 5, 2014. Pooled odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association by using the fixed or random effect model. RESULTS: Fifteen separate studies including 2,700 cases and 2,365 controls were included in the meta-analysis. We did not detect a significant association between APOE gene ?2/?3/?4 polymorphism and glaucoma in overall population (P?>?0.0083). In Asians, we detected an association of the ?4?4 genotype with elevated risk for glaucoma (OR?=?5.22, 95% CI?=?1.85-14.68, P?=?0.002), mainly for primary open angle glaucoma (OR?=?4.98, 95% CI?=?1.75-14.20, P?=?0.003). CONCLUSIONS: The meta-analysis suggests that APOE gene ?4?4 may be associated with elevated risk for primary open angle glaucoma in Asians. However, more epidemiologic studies based on larger sample size, case-control design and stratified by ethnicity as well as types of glaucoma are suggested to further clarify the relationship between APOE gene ?2/?3/?4 polymorphism and genetic predisposition to glaucoma.

| S-EPMC4035820 | biostudies-other

An Updated Review on the Genetics of Primary Open Angle Glaucoma.

Project description:Epidemiological studies suggest that by 2020 the prevalence of primary open angle glaucoma (POAG) is estimated to increase to 76.0 million, and to 111.8 million by 2040 globally due to the population aging. The prevalence of POAG is the highest among those of African descent, followed by Asians, and the lowest in Europeans. POAG is a genetically complex trait with a substantial fraction exhibiting a significant heritability. Less than 10% of POAG cases in the general population are caused by specific gene mutations and the remaining cases are polygenic. Quantitative traits related to POAG pathogenesis such as intra-ocular pressure (IOP), vertical cup/disc ratio (VCDR), optic disc area, and central corneal thickness (CCT) are highly heritable, and likely to be influenced at least in part by genes and show substantial variation in human populations. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) at different loci including CAV1/CAV2, TMCO1, CDKN2B-AS1, CDC7-TGFBR3, SIX1/SIX6, GAS7 and ATOH7 to be associated with POAG and its related quantitative traits (endophenotypes). The chapter provides a brief overview on the different GWAS and SNP association studies and their correlation with various clinical parameters important for POAG in the population worldwide, including the Middle East.

| S-EPMC4691082 | biostudies-literature

Metabolomics in Primary Open Angle Glaucoma: A Systematic Review and Meta-Analysis

Project description:Glaucoma is a leading cause of blindness worldwide. It is suggested that primary open angle glaucoma (POAG), the most common form of glaucoma, may be associated with significant metabolic alternations, but the systemic literature review and meta-analysis in the area have been missing. Altered metabolomic profiles in the aqueous humor and plasma may serve as possible biomarkers for early detection or treatment targets. In this article, we performed a systematic meta-analysis of the current literature surrounding the metabolomics of patients with POAG and metabolites associated with the disease. Results suggest several metabolites found to be specifically altered in patients with POAG, suggesting broad generalizability and pathways for future research.

| S-EPMC9135181 | biostudies-literature

Meta-Analysis of Dyslipidemia and Blood Lipid Parameters on the Risk of Primary Open-Angle Glaucoma.

Project description:ObjectiveWe aimed to explore the effect of blood lipid parameters on the risk of primary open-angle glaucoma (POAG) by meta-analysis.MethodsThe databases of PubMed, Scopus, CNKI, and Wanfang were systematically searched from inception to April 2022, and the relevant research literature was obtained, screened, and analyzed.ResultsA total of 15 studies were included in this meta-analysis, including 11 reporting dyslipidemia and risk of POAG and 5 reporting specific lipid level and risk of POAG. Dyslipidemia increased the risk of POAG with an odd ratio (OR) of 1.25 (95% CI: 1.23, 1.26). Total triglyceride and total cholesterol were not related to the prevalence of POAG, but high-density lipoprotein cholesterol was significantly negatively correlated with the risk of POAG with an OR of 0.96 (95% CI: 0.94, 0.99).ConclusionDyslipidemia is a risk factor for POAG. Given the small sample size and significant interstudy heterogeneity, additional studies are needed to establish this conclusion.

| S-EPMC9519322 | biostudies-literature

Primary open-angle glaucoma genes.

Project description:A substantial fraction of glaucoma has a genetic basis. About 5% of primary open angle glaucoma (POAG) is currently attributed to single-gene or Mendelian forms of glaucoma (ie glaucoma caused by mutations in myocilin or optineurin). Mutations in these genes have a high likelihood of leading to glaucoma and are rarely seen in normal subjects. Other cases of POAG have a more complex genetic basis and are caused by the combined effects of many genetic and environmental risk factors, each of which do not act alone to cause glaucoma. These factors are more frequently detected in patients with POAG, but are also commonly observed in normal subjects. Additional genes that may be important in glaucoma pathogenesis have been investigated using quantitative traits approaches. Such studies have begun to identify genes that control the magnitude of important quantitative features of glaucoma that may also be important risk factors for POAG, such as central corneal thickness. Each of these different approaches to study glaucoma genetics is providing new insights into the pathogenesis of POAG.

| S-EPMC3171270 | biostudies-literature

Prevalence Ratio of Primary Angle-Closure and Primary Open-Angle Glaucoma in Asian Population: A Meta-Analysis and Multiple Meta-Regression Analysis.

Project description:PurposeTo investigate the prevalence ratio of primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) in the Asian population.MethodsSystematic searches of PubMed, Embase, and Cochrane databases for population-based studies in Asia published until August 5, 2022. We conducted a meta-analysis for PACG to POAG prevalence ratio using inverse variance-weighted random-effects meta-analyses so as to combine the study-specific measures of association. Between-study outcome variation (i.e., heterogeneity) was quantified with the I2 statistic. The multiple meta-regression analyses were performed in order to further account for the reasons for heterogeneity.ResultsTwenty studies, with a total study population of 52,522 individuals, had been conducted in 13 countries. The pooled PACG to POAG prevalence ratio was 2.204 (95% confidence interval, 1.617-3.004) with high heterogeneity (p < 0.001). In multiple meta-regression model, prevalence of POAG is the most important predictor for heterogeneity (model importance, 0.954), followed continent (0.508), and publication year (0.222). For every additional elevation of POAG prevalence (i.e., increase of 1.0%), the PACG to POAG prevalence ratio is expected to rise by 0.471.ConclusionsWe estimated the pooled PACG to POAG prevalence ratio in the Asian population. The POAG prevalence is the most important factor to determine the PACG to POAG prevalence ratio.

| S-EPMC10869426 | biostudies-literature

Myocilin polymorphisms and primary open-angle glaucoma: a systematic review and meta-analysis.

Project description:BackgroundGlaucoma is the leading cause of irreversible blindness in the world. Recent evidence indicates a role for genetic susceptibility to primary open-angle glaucoma (POAG). The relation between myocilin polymorphisms and POAG susceptibility has been studied in different populations.MethodsA meta-analysis of 32 published genetic association case-control studies, which examined the relation between POAG and the R46X, R76K, Y347Y, T353I, and Q368X polymorphisms of the myocilin gene, was carried out.ResultsIn meta-analysis, significant associations were observed between POAG risk and two myocilin polymorphisms with summarized odds ratio of 4.68 (95%CI, 2.02-10.85) for Q368X and 2.17 (95% CI, 1.32-3.57) for T353I. Both Q368X and T353I were significantly associated with high-tension glaucoma, with summarized odds ratio of 4.26 (1.69, 10.73) and 2.26 (1.37-3.72). In Westerners, significant association was observed for Q368X mutation (odds ratio, 5.17; 95% CI, 2.16-12.40). However, in Asians it was for T353I (odds ratio, 2.17; 95% CI, 1.32-3.57).ConclusionsThere is strong evidence that myocilin polymorphisms are associated with POAG susceptibility, and the prevalence of myocilin mutations might be ethnicity-dependent in Caucasians for Q368X and in Asians for T353I.

| S-EPMC3460926 | biostudies-literature

Mitochondrial genome analysis of primary open angle glaucoma patients.

Project description:Primary open angle glaucoma (POAG) is a multi-factorial optic disc neuropathy characterized by accelerating damage of the retinal ganglion cells and atrophy of the optic nerve head. The vulnerability of the optic nerve damage leading to POAG has been postulated to result from oxidative stress and mitochondrial dysfunction. In this study, we investigated the possible involvement of the mitochondrial genomic variants in 101 patients and 71 controls by direct sequencing of the entire mitochondrial genome. The number of variable positions in the mtDNA with respect to the revised Cambridge Reference Sequence (rCRS), have been designated "Segregating Sites". The segregating sites present only in the patients or controls have been designated "Unique Segregating Sites (USS)". The population mutation rate (? = 4Ne?) as estimated by Watterson's ? (?w), considering only the USS, was significantly higher among the patients (p = 9.8 × 10(-15)) compared to controls. The difference in ?w and the number of USS were more pronounced when restricted to the coding region (p<1.31 × 10(-21) and p = 0.006607, respectively). Further analysis of the region revealed non-synonymous variations were significantly higher in Complex I among the patients (p = 0.0053). Similar trends were retained when USS was considered only within complex I (frequency 0.49 vs 0.31 with p<0.0001 and mutation rate p-value <1.49×10(-43)) and ND5 within its gene cluster (frequency 0.47 vs 0.23 with p<0.0001 and mutation rate p-value <4.42×10(-47)). ND5 is involved in the proton pumping mechanism. Incidentally, glaucomatous trabecular meshwork cells have been reported to be more sensitive to inhibition of complex I activity. Thus mutations in ND5, expected to inhibit complex I activity, could lead to generation of oxidative stress and favor glaucomatous condition.

| S-EPMC3733777 | biostudies-literature

Trabeculectomy and EX-PRESS Implantation in Open-Angle Glaucoma: An Updated Meta-Analysis of Randomized Controlled Trials.

Project description:PurposeAccumulating studies comparing the efficacy and safety of trabeculectomy and EX-PRESS implantation in open-angle glaucoma (OAG) report inconsistent findings. Thus, we conducted the updated meta-analysis to clarify the issue.MethodsRandomized controlled trials (RCTs) were selected through search of databases PubMed, Web of Science, Embase, and the Cochrane Library from their inception up until November 2018. The pooled mean difference (MD) for intraocular pressure reduction (IOPR) and antiglaucoma medication reduction, odds ratio (OR) for operative success, complication, and postoperative intervention was calculated using the random effects model.Results8 RCTs were enrolled, including 223 eyes in the EX-PRESS group and 217 eyes in the trabeculectomy group. EX-PRESS device implantation had a better IOPR% at 12 months postoperatively (MD = 8.9, 95% confidence interval (CI) = 2.5-15.3, P=0.006). There was no statistically significant difference in the antiglaucoma medication reduction (MD = 6.01, 95% CI = -4.13-16.15, P=0.25) and qualified success (P > 0.05). Statistically higher complete success at 1 year postoperatively was found in the EX-PRESS group (OR = 3.26, 95% CI = 1.24-8.55, P=0.02). EX-PRESS was associated with a lower frequency of increased IOP (OR = 0.15, 95% CI = 0.03-0.93, P=0.04) and hyphema (OR = 0.20, 95% CI = 0.05-0.74, P=0.02). Less postoperative intervention was needed in the EX-PRESS group (OR = 0.43, 95% CI = 0.20-0.94, P=0.04).ConclusionFor OAG patients, EX-PRESS implantation provided better efficacy in IOP control and complete success at 1 year postoperatively, with fewer increased IOP and hyphema as well as postoperative interventions. EX-PRESS device and trabeculectomy were similar in the qualified success and antiglaucoma medication reduction.

| S-EPMC6778870 | biostudies-literature

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