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Eye (Lond). 2014 Jun;28(6):662-71. doi: 10.1038/eye.2014.42. Epub 2014 Mar 7.

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

Author information

1
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2
Department of Ophthalmology, Mass Eye and Ear, Boston, MA, USA.
3
Genentech Inc., San Francisco, CA, USA.
4
Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, TN, USA.
5
Department of Ophthalmology and Hamilton Glaucoma Center, University of California at San Diego, San Diego, CA, USA.
6
Bascom Palmer Eye Institute and Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
7
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
8
Department of Ophthalmology, University of North Carolina, Chapel Hill, NC, USA.
9
1] Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA [2] Department of Medicine, Duke University Medical Center, Durham, NC, USA.
10
Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, WV, USA.
11
Eye Doctors of Washington, Chevy Chase, MD, USA.
12
Scripps Genome Center, University of California at San Diego, San Diego, CA, USA.
13
Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MD, USA.
14
Essentia Institute of Rural Health, Duluth, MN, USA.
15
Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA, USA.
16
Department of Ophthalmology, Stanford University, Palo Alto, CA, USA.
17
Department of Genetics, Stanford University, Palo Alto, CA, USA.
18
Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
19
Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA.
20
Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, IA, USA.
21
Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
22
Department of Biostatistics and Epidemiology, Harvard School of Public Health, Boston, MA, USA.
23
Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA.
24
1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Department of Ophthalmology, Mass Eye and Ear, Boston, MA, USA.

Abstract

AIMS:

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.

METHODS:

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.

RESULTS:

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.

DISCUSSION:

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.

PMID:
24603425
PMCID:
PMC4058608
DOI:
10.1038/eye.2014.42
[Indexed for MEDLINE]
Free PMC Article

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