Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma

J H Kang; S J Loomis; B L Yaspan; J C Bailey; R N Weinreb; R K Lee; P R Lichter; D L Budenz; Y Liu; T Realini; D Gaasterland; T Gaasterland; D S Friedman; C A McCarty; S E Moroi; L Olson; J S Schuman; Kuldev Singh; D Vollrath; G Wollstein; D J Zack; M Brilliant; A J Sit; W G Christen; J Fingert; J P Forman; E S Buys; P Kraft; K Zhang; R R Allingham; M A Pericak-Vance; J E Richards; M A Hauser; J L Haines; J L Wiggs; L R Pasquale

doi:10.1038/eye.2014.42

Back

Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma

Journal article

Open access

Peer reviewed

Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma

J H Kang, S J Loomis, B L Yaspan, J C Bailey, R N Weinreb, R K Lee, P R Lichter, D L Budenz, Y Liu, T Realini, …

Eye (London), Vol.28(6), pp.662-671

06/2014

DOI: 10.1038/eye.2014.42

PMCID: PMC4058608

PMID: 24603425

Files and links (1)

url

https://doi.org/10.1038/eye.2014.42View

Published (Version of record) Open Access

Abstract

Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG. We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG. The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only. Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

Genetic Predisposition to Disease

Receptors, Endothelin - genetics

Glaucoma, Open-Angle - genetics

Intraocular Pressure

Humans

Middle Aged

Glaucoma, Open-Angle - physiopathology

Caveolin 1 - genetics

Dynamins - genetics

Genotype

Male

Receptor, Endothelin B

Signal Transduction - genetics

GTP-Binding Proteins - genetics

Nitric Oxide Synthase Type III - genetics

Case-Control Studies

Endothelium, Vascular - metabolism

Female

Aged

Polymorphism, Single Nucleotide

AMP-Activated Protein Kinases - genetics

Inositol 1,4,5-Trisphosphate Receptors - genetics

Muscle, Smooth, Vascular - physiology

Details

Title: Subtitle: Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma
Creators: J H Kang - Brigham and Women's Hospital
S J Loomis - Department of Ophthalmology, Mass Eye and Ear, Boston, MA, USA
B L Yaspan - Genentech Inc., San Francisco, CA, USA
J C Bailey - Vanderbilt University
R N Weinreb - University of California, San Diego
R K Lee - University of Miami Hospital
P R Lichter - University of Michigan–Ann Arbor
D L Budenz - University of North Carolina at Chapel Hill
Y Liu - Duke University
T Realini - West Virginia University
D Gaasterland - Eye Doctors of Washington, Chevy Chase, MD, USA
T Gaasterland - Scripps Genome Center, University of California at San Diego, San Diego, CA, USA
D S Friedman - Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MD, USA
C A McCarty - Essentia Institute of Rural Health, Duluth, MN, USA
S E Moroi - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA
L Olson - Vanderbilt University
J S Schuman - Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA, USA
Kuldev Singh - Stanford University
D Vollrath - Department of Genetics, Stanford University, Palo Alto, CA, USA
G Wollstein - Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA, USA
D J Zack - Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MD, USA
M Brilliant - Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA
A J Sit - Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA
W G Christen - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
J Fingert - Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, IA, USA
J P Forman - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
E S Buys - Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
P Kraft - Department of Biostatistics and Epidemiology, Harvard School of Public Health, Boston, MA, USA
K Zhang - Department of Ophthalmology and Hamilton Glaucoma Center, University of California at San Diego, San Diego, CA, USA
R R Allingham - Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA
M A Pericak-Vance - Bascom Palmer Eye Institute and Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
J E Richards - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA
M A Hauser - Duke University
J L Haines - Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USA
J L Wiggs - Department of Ophthalmology, Mass Eye and Ear, Boston, MA, USA
L R Pasquale - Brigham and Women's Hospital
Resource Type: Journal article
Publication Details: Eye (London), Vol.28(6), pp.662-671
Publisher: England
DOI: 10.1038/eye.2014.42
PMID: 24603425
PMCID: PMC4058608
ISSN: 1476-5454
eISSN: 1476-5454
Grant note: EY013178 / NEI NIH HHS K02 DA021237 / NIDA NIH HHS EY18660 / NEI NIH HHS R56 EY011671 / NEI NIH HHS U01HG006389 / NHGRI NIH HHS EY011671 / NEI NIH HHS P30 EY014104 / NEI NIH HHS EY008208 / NEI NIH HHS R21 EY022766 / NEI NIH HHS R01 HL073389 / NHLBI NIH HHS R01 HL035464 / NHLBI NIH HHS R01 EY023512 / NEI NIH HHS HL073389 / NHLBI NIH HHS HHSN268200782096C / NHGRI NIH HHS U01 CA049449 / NCI NIH HHS R01 EY022746 / NEI NIH HHS EY144428 / NEI NIH HHS R01 EY018660 / NEI NIH HHS EY09611 / NEI NIH HHS EY010886 / NEI NIH HHS R01 EY015872 / NEI NIH HHS U10 EY012118 / NEI NIH HHS U01 HG004446 / NHGRI NIH HHS HG005259-01 / NHGRI NIH HHS P01 CA087969 / NCI NIH HHS R01 EY009611 / NEI NIH HHS HG004424 / NHGRI NIH HHS EY009847 / NEI NIH HHS EY144448 / NEI NIH HHS HL35464 / NHLBI NIH HHS R01 EY009847 / NEI NIH HHS EY015473 / NEI NIH HHS U01 HG004424 / NHGRI NIH HHS CA49449 / NCI NIH HHS R01 EY009580 / NEI NIH HHS R01 EY022306 / NEI NIH HHS HG004446 / NHGRI NIH HHS R01 EY013178 / NEI NIH HHS R01 EY019126 / NEI NIH HHS HG004608 / NHGRI NIH HHS R01 EY011405 / NEI NIH HHS EY009149 / NEI NIH HHS R01 EY011671 / NEI NIH HHS 3R01EY019126-02S1 / NEI NIH HHS R03 EY015682 / NEI NIH HHS R01 EY022305 / NEI NIH HHS R01EY022746 / NEI NIH HHS R01 EY015473 / NEI NIH HHS R01 EY015543 / NEI NIH HHS UL1 RR025758 / NCRR NIH HHS R01 EY008208 / NEI NIH HHS HHSN268200782096C / NHLBI NIH HHS UL1 TR000427 / NCATS NIH HHS EY13315 / NEI NIH HHS EY011008 / NEI NIH HHS P01 CA87969 / NCI NIH HHS 3R01EY015872-05S1 / NEI NIH HHS EY006827 / NEI NIH HHS UM1 CA167552 / NCI NIH HHS EY015682 / NEI NIH HHS U01 HG004608 / NHGRI NIH HHS EY012118 / NEI NIH HHS U01 HG004728 / NHGRI NIH HHS UL1TR000427 / NCATS NIH HHS R01 EY013315 / NEI NIH HHS EY015543 / NEI NIH HHS U01 HG006389 / NHGRI NIH HHS EY09580 / NEI NIH HHS R01 CA049449 / NCI NIH HHS R01 EY010886 / NEI NIH HHS R01 EY011008 / NEI NIH HHS R01 EY012118 / NEI NIH HHS HG004728 / NHGRI NIH HHS
Language: English
Date published: 06/2014
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980051902771

Metrics

18 Record Views

14 Times Cited - Web of Science

See more details