Journal ArticleDOI
Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma.
Gudmar Thorleifsson,Kristinn P. Magnusson,Patrick Sulem,G. Bragi Walters,Daniel F. Gudbjartsson,Hreinn Stefansson,Thorlakur Jonsson,Adalbjorg Jonasdottir,Aslaug Jonasdottir,Gerdur Stefansdottir,Gisli Masson,Gudmundur A. Hardarson,H. Petursson,Arsaell Arnarsson,Mehdi Motallebipour,Ola Wallerman,Claes Wadelius,Jeffrey R. Gulcher,Unnur Thorsteinsdottir,Augustine Kong,Fridbert Jonasson,Kari Stefansson +21 more
TLDR
Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association with glaucoma, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS).Abstract:
Glaucoma is a leading cause of irreversible blindness A genome-wide search yielded multiple single-nucleotide polymorphisms (SNPs) in the 15q241 region associated with glaucoma Further investigation revealed that the association is confined to exfoliation glaucoma (XFG) Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS) About 25% of the general population is homozygous for the highest-risk haplotype, and their risk of suffering from XFG is more than 100 times that of individuals carrying only low-risk haplotypes The population-attributable risk is more than 99% The product of LOXL1 catalyzes the formation of elastin fibers found to be a major component of the lesions in XFGread more
Citations
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Journal ArticleDOI
Biological effect of LOXL1 coding variants associated with pseudoexfoliation syndrome.
Shiwani Sharma,Sarah Martin,Matthew J. Sykes,Alpana Dave,Alex W. Hewitt,Kathryn P. Burdon,Maurizio Ronci,Nicolas H. Voelcker,Jamie E Craig +8 more
TL;DR: It is shown through molecular modelling that positions 141 and 153 are likely surface residues and hence possible recognition sites for protein-protein interactions; the Arg141Leu and Gly153Asp substitutions cause charge changes that would lead to local differences in protein electrostatic potential and in turn the potential to modify protein- protein interactions.
Journal ArticleDOI
Glaucoma Genetics: Recent Advances and Future Directions.
Tin Aung,Chiea Chuen Khor +1 more
TL;DR: It is hoped that the genetic findings could point to potential routes of therapy beyond that of intraocular pressure–lowering medications or surgery, and much further work remains to definitively link the implicated genetic variants with glaucoma causation.
Journal ArticleDOI
Retrobulbar hemodynamic parameters in pseudoexfoliation syndrome and pseudoexfoliative glaucoma
TL;DR: The results of this study showed that the retrobulbar hemodynamics might be disturbed in patients with PXG, especially in the central retinal artery.
Journal ArticleDOI
GWAS links variants in neuronal development and actin remodeling related loci with pseudoexfoliation syndrome without glaucoma.
Katarzyna Zagajewska,Magdalena Piątkowska,Krzysztof Goryca,Aneta Balabas,Anna Kluska,Agnieszka Paziewska,Ewelina Pośpiech,Iwona Grabska-Liberek,Ewa E. Hennig +8 more
TL;DR: Several new susceptibility loci for P EXS without glaucoma suggested that neuronal development and actin remodeling are potentially involved in either PEXS onset or inhibition or delay of its conversion to glau coma.
Journal ArticleDOI
Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study.
Todd E. Scheetz,Ben Faga,Lizette Ortega,Ben R. Roos,Mae O. Gordon,Michael A. Kass,Kai Wang,John H. Fingert +7 more
TL;DR: The size of the OHTS cohort and its composition of 2 large racial subgroups may limit its power to detect some glaucoma risk factors, and the Cox proportional hazard analysis demonstrated that TMCO1 alleles increased relative risk comparable with that of some previously analyzed clinical measures.
References
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Nathan Mantel,William Haenszel +1 more
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Journal ArticleDOI
The definition and classification of glaucoma in prevalence surveys
TL;DR: This review describes a scheme for diagnosis of glaucoma in population based prevalence surveys that makes provision for diagnosing glauca in eyes with severe visual loss where formal field testing is impractical, and for blind eyes in which the optic disc cannot be seen because of media opacities.
Journal ArticleDOI
Identification of a Gene That Causes Primary Open Angle Glaucoma
Edwin M. Stone,John H. Fingert,Wallace L.M. Alward,Thai Nguyen,Jon R. Polansky,Sara L.F. Sunden,Darryl Y. Nishimura,Abbot F. Clark,Arne M. Nystuen,Brian E. Nichols,David A. Mackey,Robert Ritch,Jeffrey W. Kalenak,E. Randy Craven,Val C. Sheffield +14 more
TL;DR: A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping and will aid in early diagnosis of glaucoma.