Role of cholesterol 24S-hydroxylase gene polymorphism (rs754203) in primary open angle glaucoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Mossbock G
PROVIDER: S-EPMC3049739 | biostudies-literature | 2011 Feb
REPOSITORIES: biostudies-literature
Publications
Role of cholesterol 24S-hydroxylase gene polymorphism (rs754203) in primary open angle glaucoma.
Mossböck Georg G Weger Martin M Faschinger Christoph C Schmut Otto O Renner Wilfried W Wedrich Andreas A Zimmermann Christina C El-Shabrawi Yosuf Y
Molecular vision 20110226
<h4>Purpose</h4>The enzyme cholesterol 24S-hydroxylase (Cyp46A1) is responsible for the conversion of cholesterol to its more polar metabolite 24S-hydroxycholesterol, thereby enabling the intracerebral elimination of cholesterol. An intronic single nucleotide polymorphism in the gene CYP46A1 (IVS2 -150 T>C; rs754203) has recently been associated with primary open angle glaucoma (POAG). This association, however, lacks confirmation in other studies. The purpose of the present study was to investi ...[more]
Similar Datasets
Project description:PurposeGenetic factors are shown to have a role in the development of primary open angle glaucoma (POAG). The aim of this study was to determine the effects of genetic polymorphisms of transient receptor potential melastatin (TRPM) channel genes on the risk of POAG in a Turkish population.MethodsGenomic DNA was extracted from the leukocytes of the peripheral blood, and 26 single nucleotide polymorphisms in the TRPM channel genes were analyzed in 179 patients with POAG and in 182 healthy controls of similar age by using the BioMark HD dynamic array system.ResultsThere were marked changes in the genotype (TT, 26.8%; CT, 66.7%; CC, 6.5%) and allele (T, 60.1%; C, 39.9%) frequencies for the TRPM5 gene rs34551253 (Ala456Thr, in exon 9) polymorphism in patients when compared to the controls (TT, 11.3%; CT, 74.6%; CC, 14.1%, p = 0.0009; T, 48.6%; A, 51.4%, p = 0.0063). However, no associations with the other 25 polymorphisms studied were found.ConclusionsThis is the first study to examine the involvement of TRPM channel gene variations in the risk of incident POAG. This study demonstrated that the TRPM5 gene rs34551253 (Ala456Thr) polymorphism may be associated with increased risk of developing POAG in the Turkish population.
| S-EPMC3762560 | biostudies-literature
Project description:PurposeAlterations of the plasmin system have been suggested to participate in the multifactorial pathogenesis of primary open-angle glaucoma (POAG). The main physiological inhibitor of the plasmin system is plasminogen activator inhibitor-1 (PAI-1), which leads to decreased degradation of extracellular material. Interestingly, elevated PAI-1 levels in the aqueous humor of patients with POAG have been reported. A common polymorphism within the promoter region (PAI-1 4G/5G) has previously been shown to reduce the gene transcription rate of PAI-1. The purpose of the present study was to investigate a hypothesized association between PAI-1 4G/5G and the presence of POAG in a Caucasian population.MethodsThe present case-control study comprised 212 unrelated patients with POAG and 212 healthy control subjects, matched for age and sex. Genotyping of PAI-1 4G/5G polymorphisms was done using polymerase chain reaction.ResultsAllelic frequencies and genotype distributions of PAI-1 4G/5G did not significantly differ between patients with POAG and control subjects (PAI-1 4G/5G: 29.7% versus 29.7%). Presence of the PAI-1 4G-allele was associated with a nonsignificant odds ratio of 0.98 (95% confidence interval: 0.74-1.30) for POAG.ConclusionsOur data suggest that PAI-1 4G/5G itself is unlikely to be a major risk factor among Caucasian patients with POAG.
| S-EPMC2443753 | biostudies-literature
Project description:Long non-coding RNAs were associated with the development and progression of glaucoma. Our study aim to identify the potential genes in human trabecular meshwork related to primary open-angle glaucoma (POAG).
2019-09-28 | GSE138125 | GEO
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
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
Project description:AimTo detect the mutations in two candidate genes, myocilin (MYOC) and cytochrome P450 1B1 (CYP1B1), in a Chinese family with primary open angle glaucoma (POAG).MethodsThe family was composed of three members, the parents and a daughter. All members of the family underwent complete ophthalmologic examinations. Exons of MYOC and CYP1B1 genes were screened for sequence alterations by polymerase chain reaction (PCR) and direct DNA sequencing.ResultsThe mother was the proband, she was diagnosed as POAG in both eyes. Her daughter was diagnosed as juvenile-onset POAG. The father was asymptomatic. One MYOC heterozygous mutation c.1150 G>A (D384N) in exon 3 was identified in the mother, another MYOC heterozygous variation c.1058 C>T (T353I) in exon 3 was identified in the father, and the daughter inherited both of the variations. Meanwhile, three single nucleotide polymorphisms (SNPs) in CYP1B1 gene were found in the family.ConclusionThe D384N mutation of MYOC has been reported as one of disease-causing mutations in POAG, whereas T353I variation of MYOC was thought as a high risk factor for POAG. The two variations of MYOC were first reported in one juvenile-onset POAG patient who presented with more severe clinical manifestations, suggesting that T353I polymorphism of MYOC may be associated with the severity of POAG.
| S-EPMC3693003 | biostudies-literature
Project description:The total RNA from control and POAG optic nerve lamina cribrosa region was isolated and subjected to analysis on U133A 2.0 affymetrix microarray chip. The results from these two analysis was compared to determine whether PAD II RNA level is altered. Purpose of the study. This study was done to determine which RNA transcripts undergo significant changes in the optic nerve between normal and cadaver primary open-angle glaucoma donors. Using donor tissues from NDRI we have performed proteomic analyses (which will be published shortly), we intend a comparison between the proteomic and RNA changes for select proteins in our study. Sample Collection and Preparation of Labeled Copy RNA; The total RNA from optic nerve was obtained using TRIZOL (Invitrogen Inc., Carlsbad, CA) with modification of recommended protocols. The optic nerve from donor eyes were carefully excised and minced into small pieces first using a scissor and then a scalpel. Prior to use tissue was washed with DEPC water and all solutions were prepared in DEPC water. The minced tissue was placed in a glass homogenizer with 1 ml TRIZOL per 100 mg of tissue and homogenized in a glass homogenizer DUALL 20 (Kimble Kontes Glass Co, Vineland, NJ) with 10 strokes cycles each at room temperature and after freezing with liquid nitrogen for 1 min for 40 cycles. This RNA was extracted with chloroform, isoamylalcohol and precipitated with sodium citrate/sodium chloride and isopropanol. The final air-dried RNA precipitate was suspended in DEPC water and stored in â??80oC prior to use. RNA was prepared for hybridization according to the GeneChip Expression Analysis Technical Manual (Affymetrix, Santa Clara, CA). The hybridization was performed at Gene Expression Array Core Facility at Case Western Reserve University (www.geacf.net). The RNA sample was cleaned using a column from a Qiagen RNeasy kit, (part # 74104 ) in accordance with the manufacturerâ??s instructions. The volume of DEPC water used to elute the RNA from the Qiagen column was dictated by the nominal mass of the loaded RNA sample. Samples were eluted in 100ml of water, precipitated with 0.5 volume of 7.5M Ammonium Acetate and 2.5 volumes of 100% ethanol at -20oC for 1 hr and centrifuged for 10 min at room temperature. The pellet was drained and washed twice in 500µl of 70% ethanol. Supernatant was aspirated. The pellet was dried briefly (less than 1 min) in a speeedvac (Savant) and re-suspended in a small volume (~ 12â??15ml) of DEPC water. A small aliquot (2ml) of the sample was used for quantitation. Cleaned RNA samples were annotated as â??clnRNAâ?? and stored at -20oC. cDNA Synthesis; The protocol recommended by Affymetrix Inc. for cDNA synthesis was used at all times. The reaction was primed by annealing an oligo-dT primer coupled to a T7 RNA polymerase promoter to the RNA sample. Whenever possible, 8 mg of clnRNA were reverse transcribed using Superscript II reverse transcriptase in a 20ml reaction at 42oC for 1 hr. Second strand synthesis was carried out immediately in a total reaction volume of 150ml in the presence of E. coli DNA polymerase I, RNAse H and DNA ligase. The reaction mixture incubated for 2 hrs at 16oC and for a further 5 min in the presence of T4 DNA pol.. The reaction was terminated by the addition of EDTA. The sample was cleaned with a Qiagen cDNA clean-up column according to the manufacturers directions. The elution buffer volume was 14ml. The eluted samples were stored overnight at -20oC. In-Vitro Transcription (IVT) reaction; In a 0.5ml microfuge tube, complementary RNA (cRNA) was generated in an IVT reaction using a BioArray High Yield ENZO kit (Affymetrix). The 40ml reaction contained 10ml of cDNA sample and was incubated at 37oC in the heating block for 4-5hrs. Samples were mixed by flicking, pulse-centrifuged and returned to the incubator once every 40 minutes. Upon completion of the reaction, IVT samples were adjusted to a volume of 100ml with DEPC-treated water and cleaned using Qiagen RNA clean-up columns. Samples were eluted in 45ml of DEPC-treated water. A 2ml-aliquot was used for quantitation. Corrected concentrations of cRNA (minus the input clnRNA) were determined. A standard fragmentation reaction volume was 40ml in a 0.5 ml microfuge tube and used 20mg of overall IVT RNA in 1X fragmentation buffer (40mM Tris acetate, pH 8.1, 100mM KOAc, 30mM MgOAc). The reaction was incubated at 94oC for 35min in a heat block. After the 35 min incubation the fragmented samples were placed on ice. The standard hybridization cocktail volume was 300ml. 150ml of 2X hybridization buffer was added (final concentrations : 100mM MES, 1M [Na+], 20mM EDTA, 0.01% Tween 20) Herring sperm and acetylated BSA were added to a final concentration of 0.1 and 0.5mg/ml respectively. The amount of fragmentation reaction containing 15mg of cRNA was added to the cocktail and the remaining volume was made up with molecular biology grade water. A 15ml aliquot of a 20X mixture of in-vitro transcripts of bacterial genes BioB BioC BioD and cre as external controls (spikes) were added to the cocktail to give final concentrations of 1.5, 5, 25 and 100pM respectively. Control oligonucleotide (5ml) was added to a final concentration of 50pM. Array Hybridization; Sample Hyridization cocktails (300ml) were removed from storage at â??20oC and thawed in a 45oC temperature block. The samples were incubated at 45oC for 5 min, incubated at 45oC for 5 min and then centrifuged at 15,000g for 5 min. This study used commercially available Affymetrix HG U133A 2.0 arrays only. These are in situ synthesized, high density oligonucleotide arrays which can interrogate 22,777 gene entities. The part number is 900444 more detailed information may be found at www.affymetrix.com website. Meanwhile, the affymetrix chip arrays were taken from their storage at 4oC and allowed to come to room temperature. The chamber was filled with 1X hybridization buffer (final concentrations : 100mM MES, 1M [Na+], 20mM EDTA, 0.01% Tween 20). The chip was then preconditioned by incubation in the hybridization oven at 45oC for 10 min. The chip was removed and the chamber drained. Sample cocktails (200ml) were then introduced into the chamber of the chips. The ports were sealed with tough-spots stickers and placed in the hybridization oven and incubated at 45oC with rotation overnight. Next day (16hr later), the incubation was terminated and the chips removed from the oven. Samples were retrieved from the chips and stored again in a freezer at -20oC. The chips were filled with buffer A and placed in a module of Fluidics 400 wash station. The chips were subjected to the Affymetrix â??EuKws4 ver 2â?? programmed series of stringent post hybridization washes, staining and post-staining washes in accordance with Affy protocols. Upon completion of the wash series (approximately 2 hrs), the chips were removed from the Fluidics station. The chips were inspected. Chips were scanned using an Agilent Gene Array scanner 3000 driven by Affymetrix GCOS software. Generation of Expression Values; Microarray Suite, version 5 (Affymetrix), was used to generate *.cel files, and a computer program (Probe Profiler, ver. 1.3.11; Corimbia Inc., Berkeley, CA) developed specifically for the GeneChip system (Affymetrix) was used to convert intensity data into quantitative estimates of gene expression for each probe set. The software identifies informative probe pairs, and down-weights the signal contribution of probe pairs that are subject to differential cross-hybridization effects or that consistently produce no signal. The software also detects and corrects for saturation artifacts, outliers, and chip defects. A probability statistic was generated for each probe set. The probability is associated with the null hypothesis that the expression level of the probe set is equal to zero (background). Genes not significantly expressed above background in any of the samples (P > 0.05) were
2008-06-12 | E-GEOD-2387 | biostudies-arrayexpress
Project description:PurposeTo identify the potential genes in human trabecular meshwork (TM) related to primary open-angle glaucoma (POAG).MethodsFirst, long noncoding RNA (LncRNA) and mRNA expression profiles in TM samples from 4 control subjects and 4 POAG patients were accessed by microarray analyses. Then, twenty lncRNAs were validated by real-time quantitative PCR in the same samples from microarray analyses. Finally, eight highly expressed lncRNAs were further tested by real-time quantitative PCR in TM from 8 normal controls and 19 POAG patients. Expression data were normalized and analyzed using the R software. Pathway analyses were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.ResultsA total of 2179 lncRNAs and 923 mRNAs in the TM of POAG patients were significantly upregulated, and 3111 lncRNAs and 887 mRNAs were significantly downregulated. ENST00000552367, ENST00000582505, ENST00000609130, NR_029395, NR_038379, and ENST00000586949 expression levels were significantly higher in the TM from a different cohort of POAG patient than normal controls.ConclusionENST00000552367, ENST00000582505, ENST000006091- 30, NR_029395, NR_038379, and ENST00000586949 may play essential roles in the development of POAG.
| S-EPMC8589759 | biostudies-literature
Project description:BackgroundPrimary open angle glaucoma (POAG) is considered to be a neurodegenerative optic neuropathy, in which cell death occurs by apoptosis. p21, is an important protective component of the apoptotic pathway, regulating cellular arrest in the presence of DNA damage. An unstable or altered p21 protein could modify the cellular response to genomic injury and abolish the effect of p21. A previous study on a Chinese cohort suggested that the p21 codon 31 polymorphism may alter the state of apoptosis in glaucomatous optic neuropathy, failing to protect the ganglion cells. The aim of this study was to test the hypothesis that a p21 codon 31 polymorphism is associated with POAG on a Caucasian cohort.Methods140 POAG patients and a control group of 73 healthy individuals were included in the study. All the subjects were of Caucasian origin. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique (PCR-RFLP). Patients and controls were genotyped for a single nucleotide polymorphism (C/A transversion) in the third base of codon 31 of p21, which leads to a serine (Ser)/arginine (Arg) substitution.ResultsThe distribution of the genotypes in the POAG patients showed 128 (91.4%) Ser homozygotes, 10 (7.1%) Ser/Arg heterozygotes and 2 (1.5%) Arg homozygotes. In the control cohort, there were 61 (83.6%) Ser homozygotes and 12 (16.4%) Ser/Arg heterozygotes. No Arg homozygotes were present amongst the control group. Both the allelic and genotypic frequencies of the Ser or Arg residues at codon 31 were not significantly different between POAG patients and controls (Fisher's exact test, P = 0.20 for alleles and P = 0.0561 for genotypes).ConclusionThis study suggests that the p21 codon 31 polymorphism does not contribute to the risk of POAG in the Caucasian population.
| S-EPMC1079871 | biostudies-literature
Project description:To investigate whether polymorphism rs540782 on chromsome 1, in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene, is a risk factor for primary open angle glaucoma (POAG).The study genotyped 92 unrelated POAG cases and 95 control subjects from Saudi Arabia using Taq-Man® assay.The genotype frequency distribution did not deviate significantly from the Hardy-Weinberg equilibrium (p?>?0.05). Overall, both the genotype and allele frequencies were not significantly different between cases and controls. The minor 'C' allele frequency was 49.4%, which was comparable to the Japanese population and higher than the Indian and Afro-Caribbean populations. Similarly, no significant association was found between genotypes and systemic diseases and health awareness/behavior domain variables. Importantly, glaucoma specific indices, such as intraocular pressure, cup/disc ratio and number of anti-glaucoma medication, also showed no statistically significant effect of genotypes within POAG cases.Polymorphism rs540782 is not a risk factor for POAG in the Saudi cohort.
| S-EPMC5290620 | biostudies-literature