title: Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Loomis
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, La Jolla, California.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Weinreb
authors.affiliation: Genentech, Inc., San Francisco, California.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Yaspan
authors.affiliation: Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Cooke Bailey
authors.affiliation: Eye Doctors of Washington, Chevy Chase, Maryland.
authors.forename: Douglas
authors.initials: D
authors.lastname: Gaasterland
authors.affiliation: Scripps Genome Center, University of California at San Diego, La Jolla, California.
authors.forename: Terry
authors.initials: T
authors.lastname: Gaasterland
authors.affiliation: Bascom Palmer Eye Institute and Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Lichter
authors.affiliation: Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Budenz
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia.
authors.forename: Tony
authors.initials: T
authors.lastname: Realini
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland.
authors.forename: David S
authors.initials: DS
authors.lastname: Friedman
authors.affiliation: Essentia Institute of Rural Health, Duluth, Minnesota.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan.
authors.forename: Sayoko E
authors.initials: SE
authors.lastname: Moroi
authors.affiliation: Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Lana
authors.initials: L
authors.lastname: Olson
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Schuman
authors.affiliation: Department of Ophthalmology, Stanford University, Palo Alto, California.
authors.forename: Kuldev
authors.initials: K
authors.lastname: Singh
authors.affiliation: Department of Genetics, Stanford University, Palo Alto, California.
authors.forename: Douglas
authors.initials: D
authors.lastname: Vollrath
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Gadi
authors.initials: G
authors.lastname: Wollstein
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin.
authors.forename: Murray
authors.initials: M
authors.lastname: Brilliant
authors.affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Sit
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: William G
authors.initials: WG
authors.lastname: Christen
authors.affiliation: Departments of Ophthalmology and Anatomy/Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: John
authors.initials: J
authors.lastname: Fingert
authors.affiliation: Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Harvard University, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Department of Ophthalmology and Hamilton Glaucoma Center, University of California, San Diego, La Jolla, California.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.affiliation: Bascom Palmer Eye Institute and Human Genomics, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Richards
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.affiliation: Center for Human Genetics Research, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.affiliation: 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.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. Electronic address: janey_wiggs@meei.harvard.edu.
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics*; D051243:Caveolin 2 / Q000235:genetics*; D005260:Female; D056914:Genomic Structural Variation; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D014786:Vision Disorders / Q000235:genetics*; D014794:Visual Fields
chemical_list: C495540:CAV1 protein, human; C495544:CAV2 protein, human; D051242:Caveolin 1; D051243:Caveolin 2