Journal article
Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss
Ophthalmology (Rochester, Minn.), Vol.121(2), pp.508-516
02/2014
DOI: 10.1016/j.ophtha.2013.09.012
PMCID: PMC3937766
PMID: 24572674
Abstract
The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. Case-control study. We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7 × 10(-4) was used to account for multiple comparisons. Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61 × 10(-7)). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59 × 10(-5)). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07 × 10(-4)), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.
Details
- Title: Subtitle
- Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss
- Creators
- Stephanie J Loomis - Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MassachusettsJae H Kang - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MassachusettsRobert N Weinreb - Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, La Jolla, CaliforniaBrian L Yaspan - Genentech, Inc., San Francisco, CaliforniaJessica N Cooke Bailey - Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TennesseeDouglas Gaasterland - Eye Doctors of Washington, Chevy Chase, MarylandTerry Gaasterland - Scripps Genome Center, University of California at San Diego, La Jolla, CaliforniaRichard K Lee - Bascom Palmer Eye Institute and Human Genomics, University of Miami Miller School of Medicine, Miami, FloridaPaul R Lichter - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MichiganDonald L Budenz - Department of Ophthalmology, University of North Carolina, Chapel Hill, North CarolinaYutao Liu - Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; Department of Medicine, Duke University Medical Center, Durham, North CarolinaTony Realini - Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, West VirginiaDavid S Friedman - Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MarylandCatherine A McCarty - Essentia Institute of Rural Health, Duluth, MinnesotaSayoko E Moroi - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MichiganLana Olson - Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TennesseeJoel S Schuman - Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PennsylvaniaKuldev Singh - Stanford UniversityDouglas Vollrath - Department of Genetics, Stanford University, Palo Alto, CaliforniaGadi Wollstein - Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PennsylvaniaDonald J Zack - Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MarylandMurray Brilliant - Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WisconsinArthur J Sit - Department of Ophthalmology, Mayo Clinic, Rochester, MinnesotaWilliam G Christen - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MassachusettsJohn Fingert - Departments of Ophthalmology and Anatomy/Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IowaPeter Kraft - Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Harvard University, Boston, MassachusettsKang Zhang - Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, La Jolla, CaliforniaR Rand Allingham - Department of Ophthalmology, Duke University Medical Center, Durham, North CarolinaMargaret A Pericak-Vance - Bascom Palmer Eye Institute and Human Genomics, University of Miami Miller School of Medicine, Miami, FloridaJulia E Richards - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MichiganMichael A Hauser - Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; Department of Medicine, Duke University Medical Center, Durham, North CarolinaJonathan L Haines - Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TennesseeLouis R Pasquale - Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MassachusettsJaney L Wiggs - Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. Electronic address: janey_wiggs@meei.harvard.edu
- Resource Type
- Journal article
- Publication Details
- Ophthalmology (Rochester, Minn.), Vol.121(2), pp.508-516
- DOI
- 10.1016/j.ophtha.2013.09.012
- PMID
- 24572674
- PMCID
- PMC3937766
- NLM abbreviation
- Ophthalmology
- ISSN
- 0161-6420
- eISSN
- 1549-4713
- Publisher
- United States
- Grant note
- EY013178 / NEI NIH HHS EY18660 / NEI NIH HHS CA87969 / NCI NIH HHS EY011671 / NEI NIH HHS P30 EY014104 / NEI NIH HHS EY008208 / NEI NIH HHS R21 EY022766 / NEI NIH HHS HL073389 / NHLBI NIH HHS EY144428 / NEI NIH HHS R01 EY018660 / NEI NIH HHS EY010886 / NEI NIH HHS HL73042 / NHLBI NIH HHS HG005259-01 / NHGRI NIH HHS EY009847 / NEI NIH HHS EY144448 / NEI NIH HHS R01 EY009847 / NEI NIH HHS EY015473 / NEI NIH HHS CA49449 / NCI NIH HHS R01 EY009580 / NEI NIH HHS R01 EY022306 / NEI NIH HHS U10 EY009149 / NEI NIH HHS R01 EY014428 / NEI NIH HHS RR015574 / NCRR NIH HHS R01 EY019126 / NEI NIH HHS HG004608 / NHGRI NIH HHS R01 EY011405 / NEI NIH HHS EY009149 / NEI NIH HHS EY022766 / NEI NIH HHS R01 EY011671 / NEI NIH HHS R03 EY015682 / NEI NIH HHS R01 EY022305 / NEI NIH HHS R01 EY015473 / NEI NIH HHS R01 EY015543 / NEI NIH HHS U01-HG004424 / NHGRI NIH HHS U10 EY010379 / NEI NIH HHS R01 EY008208 / NEI NIH HHS UL1 TR000427 / NCATS NIH HHS EY13315 / NEI NIH HHS EY011008 / NEI NIH HHS 3R01EY015872-05S1 / NEI NIH HHS EY015872 / NEI NIH HHS EY006827 / NEI NIH HHS UM1 CA167552 / NCI NIH HHS EY015682 / NEI NIH HHS U01 HG004608 / NHGRI NIH HHS HHSN268200782096C / PHS HHS EY012118 / NEI NIH HHS U01 HG004728 / NHGRI NIH HHS EY015543 / NEI NIH HHS EY09580 / NEI NIH HHS R01 EY010886 / NEI NIH HHS R01 EY012118 / NEI NIH HHS HG004728 / NHGRI NIH HHS R01 EY014448 / NEI NIH HHS
- Language
- English
- Date published
- 02/2014
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983979977502771
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