Distribution of COL8A2 and COL8A1 gene variants in Caucasian primary open angle glaucoma patients with thin central corneal thickness

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Distribution of COL8A2 and COL8A1 gene variants in Caucasian primary open angle glaucoma patients with thin central corneal thickness

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dc.contributor.author Desronvil, T.
dc.contributor.author Logan-Wyatt, D.
dc.contributor.author Abdrabou, W.
dc.contributor.author Triana, M.
dc.contributor.author Taheri, S.
dc.contributor.author Del Bono, E.
dc.contributor.author Olivier, M.
dc.contributor.author Jones, Richard Norman
dc.contributor.author Pasquale, Louis
dc.contributor.author Haines, J. L.
dc.contributor.author Fan, Baojian
dc.contributor.author Wiggs, Janey Lee
dc.date.accessioned 2011-04-23T18:09:15Z
dc.date.issued 2010
dc.identifier.citation Desronvil, T., D. Logan-Wyatt, W. Abdrabou, M. Triana, R. Jones, S. Taheri, E. Del Bono, et al. 2010. Distribution of COL8A2 and COL8A1 gene variants in Caucasian primary open angle glaucoma patients with thin central corneal thickness. Molecular Vision 16: 2185-2191. en_US
dc.identifier.issn 1090-0535 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4874822
dc.description.abstract Purpose: One approach to identify genes that contribute to common complex ocular disorders such as primary open angle glaucoma (POAG) is to study the genetic determinates of endophenotypes that are defined by underlying pre-disposing heritable quantitative traits such as central corneal thickness (CCT). Collagen VIII is a major component of Descemet’s membrane and studies in mice have indicated that targeted inactivation of the genes encoding the collagen type 8 alpha1 (Col8a1) and collagen type 8 alpha2 (Col8a2) subunits (COL8A1 and COL8A2) results in thinning of the corneal stroma and of Descemet’s membrane. The purpose of this study is to evaluate COL8A1 and COL8A2 as candidate genes for thin CCT in human POAG patients. Methods: 100 Caucasian POAG patients were enrolled in this study. The entire COL8A1 and COL8A2 coding sequence was determined in 8 patients with CCT<513 µm (one standard deviation (36 microns) below the mean (550 microns) and 8 patients with CCT>586 µm (one standard deviation above the mean). Selected COL8A2 exons containing variants of interest were sequenced in the full POAG cohort. Association and quantitative trait analyses were performed. Results: Three patients with CCT less than 513 µm and advanced POAG were found to have missense changes in COL8A2; two patients had a previously identified mutation, R155Q and one had a novel change, P678L (p=0.0035, Fisher’s exact test). Missense changes were not found in any of the patients with CCT>513 µm and missense changes in the COL8A1 gene were not found in any patient. One common COL8A2 SNP, rs274754 was also statistically associated with CCT (p=0.018). Conclusions: In this study we have identified COL8A2 missense changes in a group of Caucasian patients with very thin CCT and advanced POAG. These results suggest that DNA sequence variants in the COL8A2 gene may be associated with thin corneas in some glaucoma patients. Further study of COL8A2 variants in other patient populations, especially those with thinner CCT such as African-Americans would provide further support for a role of COL8A2 in corneal thickness and in glaucoma. en_US
dc.language.iso en_US en_US
dc.publisher Molecular Vision en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994337/pdf/ en_US
dc.relation.hasversion http://www.molvis.org/molvis/v16/a234 en_US
dash.license LAA
dc.title Distribution of COL8A2 and COL8A1 gene variants in Caucasian primary open angle glaucoma patients with thin central corneal thickness en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Molecular Vision en_US
dash.depositing.author Jones, Richard Norman
dc.date.available 2011-04-23T18:09:15Z
dash.affiliation.other HMS^Medicine- Beth Israel-Deaconess en_US
dash.affiliation.other HMS^Ophthalmology en_US
dash.affiliation.other HMS^Ophthalmology en_US
dash.affiliation.other HMS^Ophthalmology en_US

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