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Ophthalmology. 2014 Feb;121(2):508-16. doi: 10.1016/j.ophtha.2013.09.012. Epub 2013 Oct 25.

Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss.

Author information

1
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
2
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
3
Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, La Jolla, California.
4
Genentech, Inc., San Francisco, California.
5
Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee.
6
Eye Doctors of Washington, Chevy Chase, Maryland.
7
Scripps Genome Center, University of California at San Diego, La Jolla, California.
8
Bascom Palmer Eye Institute and Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
9
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan.
10
Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina.
11
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; Department of Medicine, Duke University Medical Center, Durham, North Carolina.
12
Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia.
13
Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland.
14
Essentia Institute of Rural Health, Duluth, Minnesota.
15
Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
16
Department of Ophthalmology, Stanford University, Palo Alto, California.
17
Department of Genetics, Stanford University, Palo Alto, California.
18
Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin.
19
Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.
20
Departments of Ophthalmology and Anatomy/Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
21
Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Harvard University, Boston, Massachusetts.
22
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
23
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, Massachusetts.
24
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. Electronic address: janey_wiggs@meei.harvard.edu.

Erratum in

  • Ophthalmology. 2014 May;121(5):1154-5.

Abstract

PURPOSE:

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.

DESIGN:

Case-control study.

PARTICIPANTS:

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).

METHODS:

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.

MAIN OUTCOME MEASURES:

Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
24572674
PMCID:
PMC3937766
DOI:
10.1016/j.ophtha.2013.09.012
[Indexed for MEDLINE]
Free PMC Article

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