Association of LOXL1 common sequence variants in german and italian patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma
Francesca Pasutto,Mandy Krumbiegel,Christian Y. Mardin,Daniela Paoli,Robert Lämmer,Bernhard H. F. Weber,Friedrich E. Kruse,Ursula Schlötzer-Schrehardt,André Reis +8 more
TLDR
Genetic variants in LOXL1 confer risk to PEX in German and Italian populations, independent of the presence of secondary glaucoma, confirming findings in patients from Northern Europe.Abstract:
Purpose Three common sequence variants in the lysyl oxidase-like 1 (LOXL1) gene were recently associated with both pseudoexfoliation (PEX) and pseudoexfoliation glaucoma (PEXG) in populations from Iceland and Sweden In this study, the genetic association of these variants was investigated in patients with PEX or PEXG of German and Italian descent Methods The three LOXL1 single-nucleotide polymorphisms (SNPs), one intronic (rs2165241) and two nonsynonymous coding SNPs (rs1048661: R141L and rs3825942: G153D) were genotyped in a total of 726 unrelated patients with PEX or PEXG (517 Germans and 209 Italians) and 418 healthy subjects who had normal findings in repeated ophthalmic examinations, and a genetic association study was performed Results Strong association with the three LOXL1 common sequence variants was seen in both the PEX and PEXG patient groups independent of their geographic origin (rs2165241, combined OR = 342, P = 128 x 10(-40); rs1048661, OR = 243, P = 290 x 10(-19); and rs3825942, OR = 487, P = 822 x 10(-23)) Similarly, the common frequent haplotype (G-G) composed of the two coding SNPs (rs1048661 and rs3825942) was strongly associated in PEX and PEXG cohorts of both populations with the disease (combined OR = 358, P = 521x 10(-43)) Conclusions Genetic variants in LOXL1 confer risk to PEX in German and Italian populations, independent of the presence of secondary glaucoma, confirming findings in patients from Northern Europeread more
Citations
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The rationale for targeting the LOX family in cancer.
TL;DR: The roles of members of the lysyl oxidase (LOX) family in the remodelling of the tumour microenvironment and their paradoxical roles in tumorigenesis and metastasis are discussed.
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Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma.
TL;DR: This review summarizes the current literature on trabecular ECM as well as the development and function of the TM and the growing number of mutations that have been identified in ECM genes and genes that modulate ECM in humans with glaucoma are documented.
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Glaucoma: genes, phenotypes, and new directions for therapy
Baojian Fan,Janey L. Wiggs +1 more
TL;DR: The human genetics and genomic approaches that have shed light on the complex inheritance of glaucoma genes and the potential for gene-based and cellular therapies that this research makes possible are summarized.
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.
References
More filters
Journal ArticleDOI
Haploview: analysis and visualization of LD and haplotype maps
TL;DR: Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface.
Journal ArticleDOI
Statistics Notes: The odds ratio
J M Bland,Douglas G. Altman +1 more
TL;DR: The odds are a way of representing probability, especially familiar for betting, and enable us to examine the effects of other variables on that relationship, using logistic regression.
Journal ArticleDOI
Lysyl oxidase: Properties, specificity, and biological roles inside and outside of the cell
TL;DR: Although the three‐dimensional structure of LO has yet to be determined, the present treatise offers hypotheses based upon its primary sequence, which may underlie the prominent electrostatic component of its unusual substrate specificity as well as the catalysis‐suppressing function of the propeptide domain of prolysyl oxidase.
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
TL;DR: 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).
Journal ArticleDOI
Elastic fiber homeostasis requires lysyl oxidase-like 1 protein.
Xiao-Qing Liu,Yun Zhao,Jiangang Gao,Basil S. Pawlyk,Barry Starcher,Jeffrey A. Spencer,Hiromi Yanagisawa,J. Zuo,Tiansen Li +8 more
TL;DR: It is shown that mice lacking the protein lysyl oxidase–like 1 (LOXL1) do not deposit normal elastic fibers in the uterine tract post partum and develop pelvic organ prolapse, enlarged airspaces of the lung, loose skin and vascular abnormalities with concomitant tropoelastin accumulation.
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