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).
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.
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.
The present meta-analysis indicated that the ε4/ε4 genotype is associated with increased risk of POAG in Asians.
"The allele and genotype frequencies of APOE gene ε2/ε3/ε4 polymorphism were extracted from fourteen separate studies [11-22,24]. Only allele frequency was extracted from the study by Ressiniotis et al. . The results of HWE test for the distribution of the genotype in control population are shown in Table 1. "
[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.
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.
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).
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.
BMC Medical Genetics 05/2014; 15(1):60. DOI:10.1186/1471-2350-15-60 · 2.08 Impact Factor
"(GLC1A) , optineurin (OPTN) on chromosome 10p15–14 (GLC1E) , and WD repeat domain 36 (WDR36) on chromosome 5q22.1 (GLC1G), which account for less than 10% of POAG cases . In addition, recent studies have shown that more than 20 other genes may contribute to POAG, such as cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) [5,6], apolipoprotein E (APOE) , optic atrophy 1 (OPA1) , neurotrophin-4 (NTF4) , interleukin-1 (IL1) , opticin (OPTC) , retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) , tumor protein p53 (p53) , ADAM metallopeptidase with thrombospondin type 1 motif, 10 (ADAMTS10) , secreted protein acidic and rich in cysteine (SPARC) , aquaporin 1 (AQP1), and solute carrier family 4, sodium bicarbonate transporter, and member 10 (SLC4A10) . However, these genes are still insufficient to explain all POAG cases, it is necessary to identify more candidate genes associated with the pathogenesis of POAG. "
[Show abstract][Hide abstract] ABSTRACT: Primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness in the world. To make progress in understanding POAG, it is necessary to identify more POAG-causing genes.
Using haplotype analysis, we found that mutational region is located on chromosome 2 in two families. Furthermore, we screened 11 candidate genes on chromosome 2 by protein-protein interaction (PPI) analysis, including mutS homolog 6 (MSH6), mutS homolog 2 (MSH2), v-rel reticuloendotheliosis viral oncogene homolog (REL), endothelial PAS domain protein 1 (EPAS1), vaccinia related kinase 2 (VRK2), F-box protein 11 (FBXO11), EGF containing fibulin-like extracellular matrix protein 1 (EFEMP1), reticulon 4 (RTN4), RAB1A, member RAS oncogene family (RAB1A), ARP2 actin-related protein 2 homolog (ACTR2), and calmodulin 2 (phosphorylase kinase, delta; CALM2). These 11 genes are all predicted to be related to trabecular meshwork changes and progressive loss of retinal ganglion cells in POAG patients.
According to our study, FBXO11 and VRK2 may interact with tumor protein p53 to regulate mitochondrial membrane permeability, mitochondrial membrane organization, and apoptosis. MSH2 is responsible for repairing DNA mismatches and RTN4 is for neuronal regeneration. Therefore, they are supposed to play a negative role in cellular process in POAG. CALM2 may be involved in retinal ganglion cell death and oxidative damage to cell communication.
The results demonstrate that the genes above may be associated with pathogenesis of POAG.
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