The Role of Apolipoprotein E Gene Polymorphisms in Primary Open-angle Glaucoma

ArticleinArchives of Ophthalmology 122(2):258-61 · March 2004with1 Reads
DOI: 10.1001/archopht.122.2.258 · Source: PubMed
To test the hypothesis that genetic polymorphisms of the apolipoprotein E (APOE) gene are associated with primary open-angle glaucoma (POAG), based on the association between neurodegenerative diseases and the APOE genotype. Genomic DNA was examined from an unrelated cohort of 137 POAG patients and 75 control subjects from the ophthalmology department of the Royal Victoria Infirmary. The APOE allele frequency (epsilon2, epsilon3, and epsilon4 alleles) was studied by polymerase chain reaction amplification of the related locus (19q13.2), enzymatic digestion of the products, gel electrophoresis, and imaging under UV illumination. For statistical analysis, we used a logistic regression model that included intraocular pressure as a continuous variable to study the possible correlation between POAG and APOE allele frequency. Logistic regression analysis showed no statistically significant association between the frequency of the APOE allele and POAG for the population studied, irrespective of the IOP (epsilon2 odds ratio, 0.82; 95% confidence interval, 0.12-5.79 [P =.84]; epsilon3 odds ratio, 0.39; 95% confidence interval, 0.10-1.49 [P =.17]; and epsilon4 odds ratio, 3.84; 95% confidence interval, 0.80-18.49 [P =.09]). In our cohort, the APOE genotype does not constitute a risk factor for developing POAG, even in patients with normal-tension glaucoma.Clinical Relevance Apolipoprotein E polymorphisms do not appear to be contributory to POAG.
    • "In Figure 1, the study inclusion process in this meta-analysis is described. Twelve studies (1,971 cases, 1,756 controls) were included [26-37]. Among them, five studies were performed in Asians (1,064 cases and 813 controls) and seven in Caucasians (907 cases and 943 controls). "
    [Show abstract] [Hide abstract] 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 ε4/ε4 versus ε3/ε3 (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 ε2/ε2 versus ε3/ε3, ε2/ε3 versus ε3/ε3, ε2/ε4 versus ε3/ε3, ε3/ε4 versus ε3/ε3, allele ε2 versus allele ε3, and allele ε4 versus allele ε3. Subgroup analyses showed that a statistically significant association between the APOE gene and the risk of POAG existed in the genetic model of ε4/ε4 versus ε3/ε3 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 ε4/ε4 genotype is associated with increased risk of POAG in Asians.
    Full-text · Article · Jul 2014
    • "In the study by Song et al. [27], the authors did not include all available published studies. Five eligible studies were not include in the meta-analysis [13,15,17,21,23] . Meanwhile , two studies contained overlapping data [19,39], and only the largest study [19] should be selected for the analysis. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Epidemiological studies have evaluated the association between Apolipoprotein E (APOE) gene ε2/ε3/ε4 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 ε2/ε3/ε4 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 ε2/ε3/ε4 polymorphism and glaucoma in overall population (P > 0.0083). In Asians, we detected an association of the ε4ε4 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 ε4ε4 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 ε2/ε3/ε4 polymorphism and genetic predisposition to glaucoma.
    Full-text · Article · May 2014
    • "On the contrary, Lam and his colleagues [13] reported that the Apo E e4 gene confers a protective effect against NTG. Their findings, however, could not be replicated in other researchers [14,15,16,17,18,19,20]. As a result, the role of Apo E in POAG remains to be established. "
    [Show abstract] [Hide abstract] ABSTRACT: A number of case-control studies were conducted to investigate the association of apolipoprotein E (Apo E) polymorphisms with primary open angle glaucoma (POAG). But the results remain controversial. This meta-analysis aims to comprehensively evaluate the relationship between a common ε2/ε3/ε4 polymorphism in Apo E gene on the risk of POAG. A comprehensive literature search for studies published up to April 2013 was performed. Summary odds ratios (ORs) and 95% confidence intervals (CI) were calculated employing random-effects models irrespective of between-study heterogeneity. Publication bias of literatures was evaluated using funnel plots and Egger's test. A total of 12 studies including 1916 cases and 1756 controls meeting the predefined criteria were involved in this meta-analysis. Overall, the Apo E ε2 allele and ε4 allele were not associated with POAG, compared with those carrying ε3 allele, with ORs of 0.98 (95% CI, 0.79 to 1.23; P = 0.872) and 1.05 (95% CI, 0.78 to 1.41; P = 0.743), respectively. Genotypic analysis also found no significant association between the ε4 carriers (ε3/ε4+ε4/ε4), ε2 carriers (ε2/ε3+ε2/ε2) and POAG, compared with participants with Apo E ε3/3, with ORs of 0.91 (95% CI, 0.66 to 1.25; P = 0.543) and 1.08 (95% CI, 0.74 to 1.57; P = 0.694), respectively. In the subgroup analysis by ethnicity, source of controls, genotyping methods, Hardy-Weinberg equilibrium or not, or type of the POAG, still no obvious associations were found. This meta-analysis suggests that Apo E ε2/ε3/ε4 polymorphisms may not be associated with the risk of POAG. However, well-designed studies with larger sample size and more ethnic groups are required to further validate the results.
    Full-text · Article · Sep 2013
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