Open AccessJournal Article
Lysyl oxidase-like protein 1 (LOXL1) gene polymorphisms and exfoliation glaucoma in a Central European population
Georg Mossböck,Wilfried Renner,Christoph Faschinger,Otto Schmut,Andreas Wedrich,Martin Weger +5 more
TLDR
The data confirm the previously reported association between LOXL1 polymorphisms and XFG and extend the knowledge to a Central European population.Abstract:
PURPOSE Exfoliation syndrome (XFS) is characterized by an accumulation of abnormal extracellular material in the anterior part of the eye that frequently leads to increased intraocular pressure and glaucomatous optic neuropathy. Recently, two non-synonymous polymorphisms (rs1048661 G>T and rs3825942 G>A) of lysyl oxidase-like protein 1 (LOXL1), a monoamine oxidase that catalyzes the polymerization of tropoelastin to elastin, were found to be associated with increased risk for XFS and exfoliation glaucoma (XFG). The aim of the present study was to investigate the role of these LOXL1 variants in a Central European cohort of Caucasian patients with XFG. METHODS The present case-control study comprised of 167 unrelated patients with XFG and 170 control subjects. Genotyping of the LOXL1 rs1048661 and rs3825942 polymorphisms was done using polymerase chain reaction. RESULTS The frequency of allele G of rs1048661 as well as rs3825942 was significantly higher in patients than in controls (rs1048661: 0.841 in patients versus 0.669; p<0.001; rs3825942: 0.994 in patients versus 0.817; p<0.001). Odds ratios of 52.1 (95% confidence interval [CI]: 13.85-195.6) and 14.67 (95% CI: 3.81-56.2), respectively, were calculated for the two high-risk haplotypes GG and TG compared to the haplotype GA. CONCLUSIONS Our data confirm the previously reported association between LOXL1 polymorphisms and XFG and extend our knowledge to a Central European population.read more
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The lens capsule.
TL;DR: This review covers the development and structure of the lens capsule, lens diseases associated with mutations in extracellular matrix genes and the role of the capsule in lens function including those proposed for visual accommodation, selective permeability to infectious agents, and cell signaling.
Journal ArticleDOI
Genotype-Correlated Expression of Lysyl Oxidase-Like 1 in Ocular Tissues of Patients with Pseudoexfoliation Syndrome/Glaucoma and Normal Patients
Ursula Schlötzer-Schrehardt,Francesca Pasutto,Pascal Sommer,Ian Hornstra,Friedrich E. Kruse,Gottfried O. H. Naumann,André Reis,Matthias Zenkel +7 more
TL;DR: Findings provide evidence for LOXL1 involvement in the initial stages of abnormal fibrogenesis in PEX tissues and suggest Alterations ofLOXL1 activation, processing, and/or substrate specificity may contribute to the abnormal aggregation of elastic fiber components into characteristic PEX fibrils.
Journal ArticleDOI
Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population
Masakazu Nakano,Yoko Ikeda,Takazumi Taniguchi,Tomohito Yagi,Masahiro Fuwa,Natsue Omi,Yuichi Tokuda,Masami Tanaka,Kengo Yoshii,Masaaki Kageyama,Shigeta Naruse,Akira Matsuda,Kazuhiko Mori,Shigeru Kinoshita,Kei Tashiro +14 more
TL;DR: It turned out that 3 genetic loci probably associated with POAG have been identified, and these findings would provide the foundation for future studies to build on, such as for the metaanalysis, to reveal the molecular mechanism of the POAG pathogenesis.
Journal ArticleDOI
Molecular pathology of pseudoexfoliation syndrome/glaucoma – New insights from LOXL1 gene associations☆
TL;DR: The available data suggest that LOXL1 is differentially regulated dependent on the phase of progression of the fibrotic process, and while increased levels of LO XL1 participate in the formation of abnormal PEX fiber aggregates in the initial phase of fibrogenesis, inadequate tissue levels may promote elastotic processes in advanced stages of the disease.
Journal ArticleDOI
Major review: Exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology
TL;DR: Current knowledge of XFS pathogenesis is summarized, gaps in knowledge are identified, and areas for future research are discussed.
References
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Journal ArticleDOI
Ancestral LOXL1 variants are associated with pseudoexfoliation in Caucasian Australians but with markedly lower penetrance than in Nordic people.
Alex W. Hewitt,Alex W. Hewitt,Shiwani Sharma,Kathryn P. Burdon,Jie Jin Wang,Paul N. Baird,David P. Dimasi,David A. Mackey,David A. Mackey,Paul Mitchell,Jamie E Craig +10 more
TL;DR: Caucasian population has a 9-fold lower lifetime incidence of pseudoexfoliation syndrome compared with Nordic populations despite having similar allelic architecture at the LOXL1 locus, which strongly suggests that as yet unidentified genetic or environmental factors independent of LO XL1 strongly influence the phenotypic expression of the syndrome.
Journal ArticleDOI
The Pro-regions of Lysyl Oxidase and Lysyl Oxidase-like 1 Are Required for Deposition onto Elastic Fibers
Laetitia Thomassin,Claudio C. Werneck,Thomas J. Broekelmann,Claudine Gleyzal,Ian Hornstra,Robert P. Mecham,Pascal Sommer +6 more
TL;DR: The results showed that the pro-regions of LOX and LOXL play a significant role in directing the deposition of both enzymes onto elastic fibers by mediating interactions with tropoelastin.
Journal ArticleDOI
Epidemiology of the pseudo‐exfoliation syndrome, A review
TL;DR: There seems to be a trend towards lower debut age of PE syndrome at lower latitudes, and a standardized set-up of such works would facilitate comparison of the results, and so some guidelines have been proposed.
Journal ArticleDOI
Pseudoexfoliation syndrome in Icelandic families.
R. Rand Allingham,Margret Loftsdottir,Maria Soffia Gottfredsdottir,Erikur Thorgeirsson,Fridbert Jonasson,Thordur Sverisson,William G Hodge,Karim F Damji,Einar Stefánsson +8 more
TL;DR: Pseudoexfoliation was strongly associated with the presence of glaucoma, but was not associated with either ARMD or systemic disease in this study, which supports the hypothesis that pseudo exfoliation syndrome is genetically inherited.
Journal ArticleDOI
Is pseudoexfoliation syndrome inherited? A review of genetic and nongenetic factors and a new observation.
Karim F. Damji,Harkaran S. Bains,Einar Stefánsson,Margaret Loftsdottir,Thordur Sverrisson,Eirikur Thorgeirsson,Fridbert Jonasson,Maria Soffia Gottfredsdottir,R. Rand Allingham +8 more
TL;DR: Evidence regarding genetic and nongenetic arguments for the etiology of pseudoexfoliation is presented and evidence that support a genetic basis for PEX is presented.
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