May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Genetic Screening of LOXL1 in Exfoliation Glaucoma
J. A. Aragon-Martin; R. Ritch; J. Liebmann; C. O’Brien; K. Blaaow; F. Mercieca; K. Damji; T. Rezaie; A. Child; M. Sarfarazi
Author Affiliations & Notes
  • J. A. Aragon-Martin
    Molecular Ophthalmic Genetics Laboratory, University of Connecticut Health Center, Farmington, Connecticut
    St. George’s University of London, London, United Kingdom
  • R. Ritch
    New York Eye and Ear Infirmary, New York, New York
  • J. Liebmann
    New York Eye and Ear Infirmary, New York, New York
  • C. O’Brien
    Institute of Ophthalmology, Dublin, Ireland
  • K. Blaaow
    Institute of Ophthalmology, Dublin, Ireland
  • F. Mercieca
    St. Luke’s Hospital, Guardamangia, Malta
  • K. Damji
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada
  • T. Rezaie
    Molecular Ophthalmic Genetics Laboratory, University of Connecticut Health Center, Farmington, Connecticut
  • A. Child
    St. George’s University of London, London, United Kingdom
  • M. Sarfarazi
    Molecular Ophthalmic Genetics Laboratory, University of Connecticut Health Center, Farmington, Connecticut
  • Footnotes
    Commercial Relationships  J.A. Aragon-Martin, None; R. Ritch, None; J. Liebmann, None; C. O’Brien, None; K. Blaaow, None; F. Mercieca, None; K. Damji, None; T. Rezaie, None; A. Child, None; M. Sarfarazi, None.
  • Footnotes
    Support  M01RR-06192
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5868. doi:
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      J. A. Aragon-Martin, R. Ritch, J. Liebmann, C. O’Brien, K. Blaaow, F. Mercieca, K. Damji, T. Rezaie, A. Child, M. Sarfarazi; Genetic Screening of LOXL1 in Exfoliation Glaucoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5868.

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Abstract

Purpose: : Genetic susceptibility of exfoliation glaucoma (XFG) and exfoliation syndrome (XFS) to the LOXL1 gene variants has recently been reported. We tested 275 affected subjects and 287 matched controls for these variants.

Methods: : Single Nucleotide Polymorphisms (SNPs) of rs1048661 (R141L), rs3825942 (G153D) and rs2165241 were genotyped in 562 individuals by SNaPshot Assay. The LOXL1 gene was also sequenced in 95 affected subjects. Case-control association studies were analyzed with SNP-STAT and PLINK programs. DNA sequences were evaluated with STADEN package.

Results: : The 275 exfoliation cases (89 XFG) comprised of 171 American (mostly European background) and 104 subjects from 12 European countries. Genotypic data were analyzed separately for XFS, XFG and for Americans and Europeans. There were no significant differences between these categories for any SNPs. For the exfoliation cohort, homozygote genotypes of G/G (rs1048661), G/G (rs3825942) and T/T (rs2165241) were over-represented. Case-control allelic association for rs1048661 (p=7.19x10-14), rs3825942 (p=2.61x10-13) and rs2165241 (p=3.05x10-24) were highly significant. Two-locus haplotype frequencies of G-G for rs1048661-rs3825942 (p=1.54x10-24), G-T for rs1048661-rs2165241 (p=1.21x10-30) and G-T for rs3825942-rs2165241 (p= 1.67x10-28) were also significant. Affected cases showed a significantly higher allelic frequency of G-G-T and this specific arrangement constituted a major risk haplotype for both XFS and XFG. Seven coding exons of LOXL1 were also sequenced in 95 affected cases. In addition to the 3 above-mentioned SNPs, we also observed V373D, V385V, rs2304719, rs2304721, rs2304722, IVS3+23C>T and IVS5-64T>C in these patients. None was considered a mutation. Genotyping of these SNPs in additional exfoliation and control subjects and further evaluation of genetic association are still in progress.

Conclusions: : We confirmed a strong association with LOXL1 variants in our patients. The G alleles of rs1048661 and rs3825942 together with the T allele of rs2165241 are highly associated with XFS and XFG. The combination of G-G-T constituted a major risk haplotype for exfoliation. DNA sequencing of 95 affected subjects did not show any mutations in the LOXL1 gene.

Keywords: genetics • gene screening • clinical (human) or epidemiologic studies: risk factor assessment 
© 2008, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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