المؤلفون: Benjamin W. Darbro, Mallory R. Tollefson, Erin A. Boese, Wallace L.M. Alward, Michael J. Schnieders, John H. Fingert

المصدر: Current Eye Research. 45:91-96

مصطلحات موضوعية: congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, genetic structures, business.industry, Glaucoma, medicine.disease, eye diseases, Sensory Systems, Hypoplasia, Morbid obesity, 03 medical and health sciences, Cellular and Molecular Neuroscience, Ophthalmology, 0302 clinical medicine, Aniridia, Foveal, Diabetes mellitus, 030221 ophthalmology & optometry, medicine, sense organs, PAX6, Stem cell, business, 030217 neurology & neurosurgery

الوصف: Purpose: Aniridia is a rare congenital eye disease, characterized by a constellation of symptoms including hypoplastic irides, foveal hypoplasia, early cataract, corneal stem cell deficienc...

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::4241b8ff3062b902069dbed803a925f2Test
https://doi.org/10.1080/02713683.2019.1649704Test

المؤلفون: John H. Fingert, Edwin M. Stone, Michael G. Anderson, Robert F. Mullins, Keith D. Carter, Markus H. Kuehn, Wallace L.M. Alward, Miles J. Flamme-Wiese, Megan J Riker, Nasreen A. Syed, Carly J. van der Heide

المصدر: Ophthalmology Glaucoma. 1:132-138

مصطلحات موضوعية: Male, 0301 basic medicine, Intraocular pressure, medicine.medical_specialty, genetic structures, Glaucoma, medicine.disease_cause, Article, Aqueous Humor, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Trabecular Meshwork, Ophthalmology, medicine, Humans, Eye Proteins, Endoplasmic Reticulum Chaperone BiP, Intraocular Pressure, Myocilin, Glycoproteins, Retrospective Studies, Mutation, business.industry, DNA, General Medicine, Middle Aged, medicine.disease, Immunohistochemistry, Tissue Donors, eye diseases, Pathophysiology, Cytoskeletal Proteins, 030104 developmental biology, medicine.anatomical_structure, 030221 ophthalmology & optometry, Female, sense organs, Trabecular meshwork, business, Glaucoma, Open-Angle

الوصف: OBJECTIVE: Mutations in myocilin (MYOC) may cause either juvenile open angle glaucoma (JOAG) or adult-onset primary open angle glaucoma (POAG). MYOC encodes a glycoprotein that is normally secreted from trabecular meshwork cells that regulate intraocular pressure. Prior in vitro, transgenic rodent, and organ culture experiments have suggested that abnormal accumulation of MYOC protein within trabecular meshwork cells is a key step in glaucoma pathophysiology. We investigated the pathogenesis of MYOC glaucoma by examining a donor eye from a patient with JOAG caused by a Tyr437His MYOC mutation. DESIGN: Case-control, immunohistochemical study of a donor eye from a patient with JOAG caused by a Tyr437His MYOC mutation and age-matched control donor eyes. SUBJECTS: An eye from a 59-year-old male with JOAG caused by a Tyr437His MYOC mutation and eyes from five donors (ages 51–66) with no known ocular disease were examined. METHODS: Frozen fixed sections of the iridocorneal angle were prepared from the donor eyes of the MYOC glaucoma patient and control eyes. We used antibodies directed against MYOC, collagen IV, and BiP/GRP78 as well as wheat germ agglutinin and concanavalin A lectins to localize MYOC protein in the trabecular meshwork. MAIN OUTCOME MEASURE: Qualitative comparison of MYOC protein labeling and localization in the trabecular meshwork of donor eyes from a glaucoma patient with a MYOC mutation and from control subjects. RESULTS: Using immunohistochemistry, we detected more abundant MYOC protein within the trabecular meshwork of the MYOC glaucoma patient’s eye than in control eyes. We further localized MYOC protein within the trabecular meshwork cells of the MYOC glaucoma patient’s eye by co-labeling with the endoplasmic reticulum (ER) marker GRP78 (BiP). Little to no MYOC was identified within the trabecular meshwork cells of control eyes. Minimal extracellular MYOC was detected in both MYOC glaucoma eyes and control eyes. CONCLUSIONS: This is the first histopathological analysis of an eye from a glaucoma patient with a MYOC mutation. Furthermore, this analysis supports our model of MYOC-associated glaucoma, in which MYOC mutations cause abnormal intracellular retention of MYOC within the ER of trabecular meshwork cells as a key step towards development of glaucoma.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c9fadf8a5e502bcbb7a71ff786988edTest
https://doi.org/10.1016/j.ogla.2018.08.004Test

المؤلفون: Elliott H. Sohn, Mark A. Greiner, Andrew E. Pouw, Chunhua Jiao, Robert F. Mullins, John H. Fingert, Ian C. Han, Jessica M. Skeie, Razek Georges Coussa

المصدر: Cells
Cells, Vol 10, Iss 687, p 687 (2021)

مصطلحات موضوعية: 0301 basic medicine, collagen, descemet membrane, genetic structures, Angiogenesis, Retinal Pigment Epithelium, Review, Interphotoreceptor matrix, AMD, Bruch's membrane, Retina, metalloproteinases, interphotoreceptor matrix, Extracellular matrix, Cornea, TIMP-3, 03 medical and health sciences, Macular Degeneration, 0302 clinical medicine, medicine, Humans, TGF-beta, lcsh:QH301-705.5, Retinal pigment epithelium, Neovascularization, Pathologic, Chemistry, Choroid, bruch’s membrane, General Medicine, VEGF, eye diseases, Cell biology, Extracellular Matrix, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), 030221 ophthalmology & optometry, MMP-14, Trabecular meshwork, sense organs, Bruch Membrane, MMP-9, Vitreous base

الوصف: The extracellular matrix (ECM) plays a crucial role in all parts of the eye, from maintaining clarity and hydration of the cornea and vitreous to regulating angiogenesis, intraocular pressure maintenance, and vascular signaling. This review focuses on the interactions of the ECM for homeostasis of normal physiologic functions of the cornea, vitreous, retina, retinal pigment epithelium, Bruch’s membrane, and choroid as well as trabecular meshwork, optic nerve, conjunctiva and tenon’s layer as it relates to glaucoma. A variety of pathways and key factors related to ECM in the eye are discussed, including but not limited to those related to transforming growth factor-β, vascular endothelial growth factor, basic-fibroblastic growth factor, connective tissue growth factor, matrix metalloproteinases (including MMP-2 and MMP-9, and MMP-14), collagen IV, fibronectin, elastin, canonical signaling, integrins, and endothelial morphogenesis consistent of cellular activation-tubulogenesis and cellular differentiation-stabilization. Alterations contributing to disease states such as wound healing, diabetes-related complications, Fuchs endothelial corneal dystrophy, angiogenesis, fibrosis, age-related macular degeneration, retinal detachment, and posteriorly inserted vitreous base are also reviewed.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf31962c4e2725216bdcad1a300141c0Test
https://pubmed.ncbi.nlm.nih.gov/33804633Test

المؤلفون: Janey L. Wiggs, C.M. vanDuijn, Vincent Laville, Adriana I Iglesias, Daniel I. Chasman, Bernard Rosner, Jessica N. Cooke Bailey, James F. Wilson, Michael A. Hauser, Jae H. Kang, William G. Christen, Christopher J Hammond, Hugues Aschard, Puya Gharahkhani, John H. Fingert, Alex W. Hewitt, Stuart MacGregor, Frank B. Hu, Peter Kraft, Louis R. Pasquale, Robert P. Igo, Yeunjoo E. Song, David A. Mackey, Pirro G. Hysi, Jonathan L. Haines, UK Biobank, Anthony P Khawaja, Clara C. Cousins, Reka Nagy, Veronique Vitart

المساهمون: Département de Biologie Computationnelle - Department of Computational Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Edinburgh, Case Western Reserve University [Cleveland], Harvard T.H. Chan School of Public Health, QIMR Berghofer Medical Research Institute, University of Melbourne, University of Tasmania [Hobart, Australia] (UTAS), The University of Western Australia (UWA), King‘s College London, University of Oxford [Oxford], University of Iowa [Iowa City], Duke University [Durham], University of Cambridge [UK] (CAM), Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Orkney Complex Disease Study was supported by the Chief Scientist Office of the Scottish Government (CZB/4/276, CZB/4/710), a Royal Society URF to Dr Wilson, the MRC Human Genetics Unit quinquennial programme 'QTL in Health and Disease,' Arthritis Research UK, and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947)., The Viking Health Study – Shetland (VIKING) was supported by the MRC Human Genetics Unit quinquennial programme grant 'QTL in Health and Disease.', European Project: 35103,EUROSPAN, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, Clinical Genetics, Ophthalmology

المصدر: American Journal of Ophthalmology
American Journal of Ophthalmology, Elsevier Masson, 2019, 206, pp.245-255. ⟨10.1016/j.ajo.2019.05.015⟩
American Journal of Ophthalmology, 2019, 206, pp.245-255. ⟨10.1016/j.ajo.2019.05.015⟩
American Journal of Ophthalmology, 206, 245-255. Elsevier Inc.
Am J Ophthalmol
Laville, V, Kang, J H, Cousins, C, Iglesias, A I, Nagy, R, Cooke Bailey, J N, Igo, R P, Song, Y E, Chasman, D I, Christen, W, Kraft, P & Wilson, J F & Vitart, V 2019, ' Genetic correlations between diabetes and glaucoma: an analysis of continuous and dichotomous phenotypes ', American journal of ophthalmology . https://doi.org/10.1016/j.ajo.2019.05.015Test

مصطلحات موضوعية: Male, Linkage disequilibrium, genetic structures, Glaucoma, Genome-wide association study, Type 2 diabetes, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Incidence, Aged, 80 and over, 2. Zero hunger, MESH: Aged, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Middle Aged, Incidence, MESH: Tonometry, Ocular, Middle Aged, Pedigree, 3. Good health, Europe, Phenotype, MESH: Young Adult, Female, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Glaucoma, Open-Angle, MESH: Diabetes Mellitus, Type 2, Adult, medicine.medical_specialty, Adolescent, MESH: Pedigree, Biology, MESH: Phenotype, Genetic correlation, Article, Tonometry, Ocular, Young Adult, 03 medical and health sciences, MESH: Cross-Sectional Studies, SDG 3 - Good Health and Well-being, MESH: Intraocular Pressure, Genetic linkage, Ophthalmology, medicine, MESH: United States, Humans, Intraocular Pressure, Aged, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Adult, Heritability, medicine.disease, United States, Human genetics, eye diseases, MESH: Male, Cross-Sectional Studies, Diabetes Mellitus, Type 2, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Genome-Wide Association Study, 030221 ophthalmology & optometry, MESH: Glaucoma, Open-Angle, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, sense organs, MESH: Europe, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, Genome-Wide Association Study

الوصف: Purpose A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits. Design Cross-sectional study. Methods We assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure [IOP], central corneal thickness [CCT], corneal hysteresis [CH], corneal resistance factor [CRF], cup-to-disc ratio [CDR], and primary open-angle glaucoma [POAG]). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank, and the International Glaucoma Genetics Consortium. We calculated genetic correlation (rg) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT, and select diabetes-related traits based on individual level phenotype data in 2 Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines. Results Overall, there was little rg between diabetes- and glaucoma-related traits. Specifically, we found a nonsignificant negative correlation between T2D and POAG (rg = −0.14; P = .16). Using Sequential Oligogenic Linkage Analysis Routines, the genetic correlations between measured IOP, CCT, FBS, fasting insulin, and hemoglobin A1c were null. In contrast, genetic correlations between IOP and POAG (rg ≥ 0.45; P ≤ 3.0 × 10−4) and between CDR and POAG were high (rg = 0.57; P = 2.8 × 10−10). However, genetic correlations between corneal properties (CCT, CRF, and CH) and POAG were low (rg range −0.18 to 0.11) and nonsignificant (P ≥ .07). Conclusion These analyses suggest that there is limited genetic correlation between diabetes- and glaucoma-related traits.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f37eb2ae4c5d9cebd21d3aa695a2b922Test
https://hal-pasteur.archives-ouvertes.fr/pasteur-03278624Test

المؤلفون: John H. Fingert, Carly J. Lewis, Edwin M. Stone, Wallace L.M. Alward, Adam P. DeLuca, Adam Hedberg-Buenz

المصدر: Human Molecular Genetics. 26:R28-R36

مصطلحات موضوعية: 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Pediatrics, medicine.medical_specialty, PAX6 Transcription Factor, genetic structures, CYP1B1, Glaucoma, Visual disability, Biology, 03 medical and health sciences, 0302 clinical medicine, Anterior Eye Segment, Genetics, medicine, Humans, Invited Reviews, Eye Abnormalities, Eye Proteins, Aniridia, Molecular Biology, Genetics (clinical), Homeodomain Proteins, Blindness, PITX2, Childhood blindness, Eye Diseases, Hereditary, Forkhead Transcription Factors, General Medicine, medicine.disease, eye diseases, 030104 developmental biology, Latent TGF-beta Binding Proteins, Cytochrome P-450 CYP1B1, Mutation, 030221 ophthalmology & optometry, sense organs, PAX6, Transcription Factors

الوصف: Glaucoma is the leading cause of irreversible blindness worldwide. Although most glaucoma patients are elderly, congenital glaucoma and glaucomas of childhood are also important causes of visual disability. Primary congenital glaucoma (PCG) is isolated, non-syndromic glaucoma that occurs in the first three years of life and is a major cause of childhood blindness. Other early-onset glaucomas may arise secondary to developmental abnormalities, such as glaucomas that occur with aniridia or as part of Axenfeld-Rieger syndrome. Congenital and childhood glaucomas have strong genetic bases and disease-causing mutations have been discovered in several genes. Mutations in three genes (CYP1B1, LTBP2, TEK) have been reported in PCG patients. Axenfeld-Rieger syndrome is caused by mutations in PITX2 or FOXC1 and aniridia is caused by PAX6 mutations. This review discusses the roles of these genes in primary congenital glaucoma and glaucomas of childhood.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::791dd924e5a4fb73d7bedfe1621490cdTest
https://doi.org/10.1093/hmg/ddx205Test

المؤلفون: Kathryn P. Burdon, Marianne O. Price, Natalie A. Afshari, Simon G. Gregory, Jiagang Zhao, S. Amer Riazuddin, Sanjay V. Patel, Elmer Balajonda, Sudha K. Iyengar, Christopher R. Croasdale, Jamie E Craig, Venkateswara Mootha, Gordon K. Klintworth, Barbara Truitt, John F. Stamler, George O D Rosenwasser, Shiwani Sharma, Abraham Kuot, Jonathan H. Lass, Mollie A. Minear, Richard A. Mills, Steven P. Dunn, Sonja Klebe, Keith H. Baratz, John H. Fingert, Anthony J. Aldave, Xuejun Qin, Dwight Stambolian, V. Lakshmi Pulagam, John D. Gottsch, Joan E. Bailey-Wilson, Francis W. Price, Nathan Morris, Yi-Ju Li, Robert P. Igo, J. B. Rimmler

المصدر: Nature Communications, Vol 8, Iss 1, Pp 1-8 (2017)
Nature Communications

مصطلحات موضوعية: 0301 basic medicine, Science, General Physics and Astronomy, Locus (genetics), Genome-wide association study, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Cornea, medicine, Humans, Genetics, Multidisciplinary, Fuchs' Endothelial Dystrophy, Reproducibility of Results, General Chemistry, TCF4, eye diseases, 3. Good health, Transplantation, Corneal Disorder, 030104 developmental biology, medicine.anatomical_structure, ROC Curve, Genetic Loci, 030221 ophthalmology & optometry, Etiology, sense organs, Fuchs Endothelial Corneal Dystrophy, Genome-Wide Association Study

الوصف: The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P
Fuchs endothelial corneal dystrophy (FECD) is one of the most common reasons for corneal transplantation, and is known to cluster in families. Here, the authors discover new genetic loci associated with FECD with sex-specific effects and implications for disease mechanism.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78aba81960472d88ac8bad9b04f110f5Test
https://doaj.org/article/d1c65f3362014583bd22c5188abefc76Test

المؤلفون: Douglas J Rhee, Bernard Rosner, Louis R. Pasquale, Yeunjoo E. Song, Hugues Aschard, Caroline C W Klaver, Allison E. Ashley-Koch, Jessica N. Cooke Bailey, Felipe A. Medeiros, Gadi Wollstein, Jonathan L. Haines, Pirro G. Hysi, Terry Gaasterland, Lisa A Hark, Richard K. Lee, Vikas Gulati, Douglas Vollrath, R. Rand Allingham, Margaret A. Pericak-Vance, Anthony P Khawaja, Julia E. Richards, William K. Scott, Murray H. Brilliant, Ching-Yu Cheng, Robert P. Igo, Joel S. Schuman, Daniel I. Chasman, Michael A. Hauser, Yutao Liu, Tony Realini, Robert N. Weinreb, Jae H. Kang, Robert Ritch, C.M. vanDuijn, Kuldev Singh, Sayoko E. Moroi, Arthur J. Sit, Donald L. Budenz, Peter Kraft, Donald J. Zack, John H. Fingert, Janey L. Wiggs, William G. Christen, Adriana I Iglesias, Shane Haven

المساهمون: Harvard Medical School [Boston] (HMS), Centre d'Études Biologiques de Chizé - UMR 7372 (CEBC), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), King‘s College London, Laboratoire Mouvement Sport Santé (M2S), École normale supérieure - Cachan (ENS Cachan)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Singapore Eye Research Institute [Singapore] (SERI), Lawrence Livermore National Laboratory (LLNL), Epidemiology, Ophthalmology, Institut National de la Recherche Agronomique (INRA)-La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-École normale supérieure - Rennes (ENS Rennes)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

المصدر: European Journal of Human Genetics
European Journal of Human Genetics, Nature Publishing Group, 2017, 25 (11), pp.1261-1267. ⟨10.1038/ejhg.2017.136⟩
European journal of human genetics : EJHG, vol 25, iss 11
European Journal of Human Genetics, 25(11), 1261-1267. Nature Publishing Group
European Journal of Human Genetics, 25, 11, pp. 1261-1267
European Journal of Human Genetics, 25, 1261-1267
European Journal of Human Genetics, 2017, 25 (11), pp.1261-1267. ⟨10.1038/ejhg.2017.136⟩

مصطلحات موضوعية: Male, 0301 basic medicine, Aging, Linkage disequilibrium, Intraocular pressure, genetic structures, Glaucoma, Blood Pressure, Genome-wide association study, Neurodegenerative, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Linkage Disequilibrium, 0302 clinical medicine, Medicine, Genetics (clinical), Genetics & Heredity, Genetics, [STAT.AP]Statistics [stat]/Applications [stat.AP], MESH: Genetic Predisposition to Disease, MESH: Blood Pressure, 3. Good health, Open-Angle, MESH: Linkage Disequilibrium, Female, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Glaucoma, Open-Angle, medicine.medical_specialty, Open angle glaucoma, Clinical Sciences, International Glaucoma Genetics Consortium, Genetic correlation, Article, 03 medical and health sciences, MESH: Intraocular Pressure, Ophthalmology, Humans, Genetic Predisposition to Disease, Eye Disease and Disorders of Vision, Intraocular Pressure, MESH: Humans, business.industry, Human Genome, Neurosciences, Heritability, medicine.disease, MESH: Male, eye diseases, 030104 developmental biology, Blood pressure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030221 ophthalmology & optometry, MESH: Glaucoma, Open-Angle, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, sense organs, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, MESH: Female

الوصف: Item does not contain fulltext 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 x 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 x 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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::960769d0fdf5971c00cc3da58c318ebbTest
https://doi.org/10.1038/ejhg.2017.136Test

المؤلفون: Mae O. Gordon, Ben Faga, Ben R. Roos, John H. Fingert, Michael A. Kass, Todd E. Scheetz, Kai Wang, Lizette Ortega

المصدر: Ophthalmology. 123:2527-2536

مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Intraocular pressure, Genotype, Genotyping Techniques, genetic structures, Black People, Ocular hypertension, Glaucoma, Polymorphism, Single Nucleotide, White People, Article, Cohort Studies, Tonometry, Ocular, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Risk Factors, Ophthalmology, Internal medicine, medicine, Humans, Allele frequency, Alleles, Intraocular Pressure, business.industry, Proportional hazards model, Membrane Proteins, Middle Aged, medicine.disease, eye diseases, 030104 developmental biology, Relative risk, Cohort, 030221 ophthalmology & optometry, Female, Ocular Hypertension, Calcium Channels, sense organs, business, Glaucoma, Open-Angle, Cohort study

الوصف: Purpose Primary open-angle glaucoma (POAG) is a major cause of blindness and visual disability. Several genetic risk factors for POAG and optic nerve features have been identified. We measured the relative risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS). Design Comparative series. Participants One thousand fifty-seven of 1636 participants (65%) of the OHTS were enrolled in this genetics ancillary study. Methods Samples of DNA were available from 1057 OHTS participants. Of these, 209 developed POAG (cases) and 848 did not develop glaucoma (controls) between 1994 and 2009. The frequencies of 13 risk alleles previously associated with POAG or with optic disc features in other cohorts were compared between POAG cases and controls in the OHTS cohort using analyses of variance. The 2 largest subgroups, non-Hispanic whites (n = 752; 70.7%) and blacks (n = 249, 23.7%), also were analyzed separately. The probability of glaucoma developing over the course of the OHTS was compared between participants stratified for transmembrane and coiled-coil domains 1 ( TMCO1 ) risk alleles using Kaplan-Meier and Cox proportional hazards analyses. Main Outcome Measures Association of POAG with known genetic factors. Results No association was detected between the known POAG risk alleles when the OHTS cohort was examined as a whole. However, in the subgroup of non-Hispanic whites, allele frequencies at the TMCO1 locus were statistically different between cases and controls ( P = 0.00028). By 13 years, non-Hispanic white participants with TMCO1 risk alleles had a 12% higher cumulative frequency of glaucoma developing than participants with no TMCO1 risk alleles. Moreover, the Cox proportional hazard analysis demonstrated that TMCO1 alleles increased relative risk comparable with that of some previously analyzed clinical measures (i.e., intraocular pressure). Conclusions The size of the OHTS cohort and its composition of 2 large racial subgroups may limit its power to detect some glaucoma risk factors. However, TMCO1 genotype was found to increase the risk of glaucoma developing among non-Hispanic whites, the largest racial subgroup in the OHTS cohort, at a magnitude similar to clinical predictors of disease that long have been associated with glaucoma.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c015d45b5a6c5ea80d1bb09c079f944fTest
https://doi.org/10.1016/j.ophtha.2016.08.036Test

المؤلفون: Anamika Tandon, Wallace L.M. Alward, Young H. Kwon, John H. Fingert, Ze Zhang, Kai Wang

المصدر: Am J Ophthalmol

مصطلحات موضوعية: Adult, Male, Intraocular pressure, medicine.medical_specialty, genetic structures, Adolescent, Ocular hypertension, Glaucoma, Transillumination, Slit Lamp Microscopy, Article, 03 medical and health sciences, Tonometry, Ocular, Young Adult, 0302 clinical medicine, Trabecular Meshwork, Ophthalmology, Medicine, Humans, Genetic Predisposition to Disease, Prospective Studies, Prospective cohort study, Child, Intraocular Pressure, 030304 developmental biology, Aged, 0303 health sciences, business.industry, food and beverages, Middle Aged, medicine.disease, eye diseases, Pedigree, medicine.anatomical_structure, Cross-Sectional Studies, Pigment dispersion syndrome, 030221 ophthalmology & optometry, Optic nerve, Female, sense organs, Trabecular meshwork, business, Glaucoma, Open-Angle, Follow-Up Studies

الوصف: Purpose Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are presumed to be inherited in an autosomal dominant manner. We examine relatives of patients with PDS and PG in order to determine the heritability of these diseases. Design This was a prospective, cross-sectional study. Methods One hundred and one patients with PDS were prospectively recruited over 11 months. Four of the patients had PDS without ocular hypertension or glaucoma, 6 had PDS and ocular hypertension, and 91 had PG. Criteria for PDS were 2 of 3 signs: Krukenberg spindle, midperipheral iris transillumination defects, and/or heavy trabecular meshwork pigmentation. Criteria for PG were PDS and 2 of 3 signs: intraocular pressure >21 mm Hg, glaucomatous optic nerve damage, and/or glaucomatous visual field loss. Ninety-nine first-degree relatives living within a 100-mile radius of Iowa City, Iowa were examined in the clinic to determine the probability of familial transmission. Results A total of 10 of 99 (10.10%) first-degree relatives were diagnosed with PDS (1 with PDS alone, 2 with PDS and ocular hypertension, and 7 with PG). Seven families with ≥2 affected members were identified. The majority of affected family members (8/10) showed moderate to heavy trabecular meshwork pigmentation and either Krukenberg spindle or transillumination defects. Conclusions Most of the cases of PDS in our study were sporadic, and the risk to first-degree relatives is lower than previously reported. However, there are families with apparent autosomal dominant inheritance of PDS in which the risk to relatives may be high.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::809c4067c9f087aad75b697444dde948Test
https://pubmed.ncbi.nlm.nih.gov/30796891Test

المؤلفون: R. Rand Allingham, Julia E. Richards, William K. Scott, Janey L. Wiggs, Jessica N. Cooke Bailey, Robert Ritch, Michael A. Hauser, Arthur J. Sit, Joel S. Schuman, Jonathan L. Haines, Donald L. Budenz, Jae H. Kang, Margaret A. Pericak-Vance, Douglas E. Gaasterland, William G. Christen, Yutao Liu, Kang Zhang, Robert N. Weinreb, Donald J. Zack, Kuldev Singh, Felipe A. Medeiros, Terry Gaasterland, Gadi Wollstein, Douglas Vollrath, Louis R. Pasquale, Tony Realini, Richard K. Lee, Anthony P Khawaja, Murray H. Brilliant, S.E. Moroi, Paul R. Lichter, John H. Fingert, Peter Kraft

المصدر: Investigative Ophthalmology & Visual Science
Khawaja, AP; Cooke Bailey, JN; Kang, JH; Rand Allingham, R; Hauser, MA; Brilliant, M; et al.(2016). Assessing the association of mitochondrial genetic variation with primary open-angle glaucoma using gene-set analyses. Investigative Ophthalmology and Visual Science, 57(11), 5046-5052. doi: 10.1167/iovs.16-20017. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/6tq4q4qpTest
Investigative ophthalmology & visual science, vol 57, iss 11

مصطلحات موضوعية: 0301 basic medicine, Genetics, genetic structures, Carbohydrate Metabolism Pathway, Lipid metabolism, Biological Sciences, Biology, Carbohydrate metabolism, Mitochondrion, Ophthalmology & Optometry, Medical and Health Sciences, eye diseases, mitochondria, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, glaucoma, Genetic variation, 030221 ophthalmology & optometry, Fatty acid elongation, genetics, sense organs, KEGG, Gene

الوصف: © 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved. PURPOSE. Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins. METHODS. We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure. RESULTS. We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010). CONCLUSIONS. We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::27ad174fa9e24c4b05e595ebdff19f71Test
http://europepmc.org/articles/PMC5040191Test