Fluctuation in systolic blood pressure is a major systemic risk factor for development of primary open-angle glaucoma.
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ABSTRACT:
SUBMITTER: Lee NY
PROVIDER: S-EPMC5338023 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
Fluctuation in systolic blood pressure is a major systemic risk factor for development of primary open-angle glaucoma.
Lee Na Young NY Jung Younhea Y Han Kyungdo K Park Chan Kee CK
Scientific reports 20170306
We evaluated the risk of development of primary open-angle glaucoma (POAG) in terms of variability in BP using a nationwide, population-based, 11-year longitudinal study using the Korean National Health Insurance Research Database. We included patients who underwent health care examinations more than twice between January 2002 and December 2006. We divided all subjects by the quartiles of variability in systolic blood pressure (SBP), diastolic blood pressure (DBP), and the difference between SBP ...[more]
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Project description:Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 × 10-27) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 × 10-5); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.
| S-EPMC5643970 | biostudies-literature
Project description:Glaucoma is a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG), the most common type, is a complex inherited disorder that is characterized by progressive retinal ganglion cell death, optic nerve head excavation, and visual field loss. The discovery of a large, and growing, number of genetic and chromosomal loci has been shown to contribute to POAG risk, which carry implications for disease pathogenesis. Differential gene expression analyses in glaucoma-affected tissues as well as animal models of POAG are enhancing our mechanistic understanding in this common, blinding disorder. In this review we summarize recent developments in POAG genetics and molecular genetics research.
| S-EPMC5557663 | biostudies-literature
Project description:Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N?=?1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.
| S-EPMC3342933 | biostudies-literature
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:PurposeThe purpose of this study was to evaluate the association of 24-hour intraocular pressure (IOP) fluctuation with corneal biomechanics and ocular biometric parameters in Chinese patients with primary open angle glaucoma (POAG) before initial treatment.MethodsForty-nine Chinese patients with POAG (98 eyes) were recruited in this study before start of any POAG treatment. The 24-hour IOP was measured with a 2-hour interval by a noncontact tonometer. Corneal biomechanical properties and biometric parameters were measured once during 8 AM to 6 PM before 24-hour IOP measurement.ResultsThe 24-hour IOP fluctuation was defined as the differences between the peak and trough IOP measurement and was significantly associated with axial length (AL) in the multivariate analysis. The POAG subjects with AL ≤ 26 mm had significantly larger 24-hour IOP fluctuation but lower corneal hysteresis, compared to those with AL > 26 mm. In addition, subgroup analysis showed that high tension glaucoma subjects had larger 24-hour IOP fluctuation and higher corneal resistance factor than patients with normal tension glaucoma.ConclusionsThis study revealed the association of 24-hour IOP fluctuation with office hour corneal biomechanical properties and AL in patients with POAG. Their contributions to IOP fluctuation should be considered in the risk analysis of glaucoma development and progression.Translational relevanceOcular biometric parameters are related with 24-hour IOP fluctuation in patients with POAG, which is potentially helpful in explaining different progression patterns in different types of patients.
| S-EPMC7683862 | biostudies-literature
Project description:PurposeTo document the diurnal intraocular pressure (IOP) profile with rebound tonometry performed by primary glaucoma patients in non-clinic environment.Patients and methodsFifty-three medically-treated eyes of 31 primary angle closure glaucoma (PACG) and 22 primary open angle glaucoma (POAG) patients with no previous eye surgery were recruited. Diurnal IOP was measured 5 times per day at four-hourly intervals from 08:00 to 24:00 for 1 week in patients' study eye using rebound tonometry in a non-clinic environment. The diurnal IOP profiles were compared between PACG and POAG eyes.ResultsFor both PACG and POAG eyes, mean patient-measured IOP was highest in the morning, gradually decreased over the course of a day, and was lowest by midnight (p < 0.001). The diurnal IOP fluctuation ± 1 standard deviation (SD), as documented by SD in daily IOP values, was lower in PACG group (1.6 ± 1.1 mmHg) than in POAG group (2.0 ± 1.2 mmHg; p = 0.049). The mean trough IOP ± 1 SD was higher in PACG group (12.9 ± 2.8 mmHg), compared to POAG group (11.5 ± 3.8 mmHg; p = 0.041). The mean IOP level at midnight ± 1 SD in PACG group (14.0 ± 3.2 mmHg) was higher than that in POAG group (12.1 ± 3.7 mmHg; p = 0.013).ConclusionsIOP in primary glaucoma patients was highest in the morning, and decreased over the course of a day in non-clinic environment. Treated diurnal IOP fluctuation seemed to be greater in POAG than PACG eyes.
| S-EPMC5363915 | 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. 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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. 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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:To investigate the association between the additive effects of genetic variants associated with intraocular pressure (IOP) and IOP, vertical cup-to-disc ratio (VCDR), and high tension glaucoma (HTG) or normal tension glaucoma (NTG) as phenotypic features of primary open-angle glaucoma (POAG), and to evaluate the clinical usefulness of the additive effects of IOP-related genetic variants for predicting IOP elevation, Japanese patients with HTG (n = 255) and NTG (n = 261) and 246 control subjects were genotyped for nine IOP-related genetic variants near CAV2, GAS7, GLCCI1/ICA1, ABCA1, ARHGEF12, FAM125B, FNDC3B, ABO, and PTPRJ/AGBL2. The total number of risk alleles of these genetic variants was calculated for each participant as a genetic risk score (GRS), and the association between the GRS and the maximum IOP, mean VCDR, and phenotype (HTG or NTG) of POAG was evaluated. As the GRS increased, the maximum IOP (P = 0.012) and VCDR (P = 0.010) significantly increased. The GRS (9.1±1.9) in patients with HTG was significantly higher (P = 0.011) than that (8.7±1.8) in control subjects. The patients with GRS?12 as a cut-off value had a 2.54 times higher (P = 0.0085) risk on HTG (maximum IOP?22mmHg) compared with all patients. The IOP-related GRS approach substantiated that the IOP and VCDR were increased by the additive effects of IOP-related genetic variants in POAG. The high IOP-related GRS in patients with HTG but not NTG shows that there are differences in the genetic background between HTG and NTG and supports the notion that the phenotype (HTG or NTG) in patients with POAG depends on the additive effects of IOP-related genetic variants. The above-mentioned cut-off value of IOP-related GRS may be clinically useful for predicting the risk of IOP elevation.
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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:This study aimed to investigate the molecular mechanism responsible for primary open-angle glaucoma (POAG) progression. We analyzed microRNAs (miRNAs) expression profiling in aqueous humor (AH) of both POAG patients and normal controls, using a microarray-based approach. Subsequently, differentially expressed miRNAs (DEmiRNAs) were identified using Bayes moderated t-test. Next, DEmiRNAs target genes were predicted based on miRNA databases, followed by GO analysis and pathway analysis using DAVID. Furthermore, OAG-related genes analysis for target genes was carried out using CTD database, respectively. Finally, verification of DEmiRNAs expression levels was performed by RT-qPCR. A total of 40 significant DEmiRNAs were identified between control and POAG groups, including 24 up-regulated miRNAs and 16 down-regulated miRNAs. Further, the target genes of hsa-miR-206, including BMP2, SMAD4, ID2, and TNF, were mainly enriched in transforming growth factor-β (TGF-β) signaling pathway. While, target genes of hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p, including BCL2, EPHB2, VEGFA, COL4A1, APC, and TGFBR1, were enriched in eye development. Moreover, FNDC3B, CAV2 and VEGF, target genes of hsa-miR-206 or hsa-miR-34c-5p, were the OAG-related genes. Ultimately, RT-qPCR analysis confirmed that mRNA levels of hsa-miR-206, hsa-miR-7-2-3p, and hsa-miR-20b-3p were increased, while those of hsa-miR-184 and hsa-miR-34c-5p were decreased in POAG compared with normal groups (P < 0.05). Hsa-miR-206, hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p might play a significant role in the pathogenesis of POAG and hsa-miR-206 might be associated with the development of POAG by regulating TGF-β signaling pathway. These results might provide insight toward a better understanding of the pathogenesis of POAG.
2015-08-04 | GSE71639 | GEO