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Ancestral LOXL1 variants are associated with pseudoexfoliation in Caucasian Australians but with markedly lower penetrance than in Nordic people


Hewitt, AW and Sharma, S and Burdon, KP and Wang, JJ and Baird, PN and Dimasi, DP and Mackey, DA and Mitchell, P and Craig, JE, Ancestral LOXL1 variants are associated with pseudoexfoliation in Caucasian Australians but with markedly lower penetrance than in Nordic people, Human Molecular Genetics, 17, (5) pp. 710-716. ISSN 0964-6906 (2008) [Refereed Article]

Copyright Statement

Copyright 2007 The Author

DOI: doi:10.1093/hmg/ddm342


Pseudoexfoliation syndrome is a generalized disorder of the extracellular matrix, characterized by the pathological accumulation of abnormal fibrillar material in the anterior segment of the eye predisposing to glaucomatous optic neuropathy. We investigated the role of lysyl oxidase-like 1 (LOXL1) sequence variation in a Caucasian Australian population-based cohort of 2508 individuals, 86 (3.4%) of whom were diagnosed with pseudoexfoliation syndrome. Two non-synonymous variants in exon 1 of LOXL1 (Arg141Leu;Gly153Asp) were found to be strongly associated with pseudoexfoliation. Two copies of the high risk haplotype at these single-nucleotide polymorphisms conferred a risk of 7.20 (95%CI: 3.04-20.75) compared with no copies of the high risk haplotype. Each of the disease-associated alleles is by far commoner in the normal population, and examination of cross-species homology reveals that the two disease-associated coding variants belong to the ancestral version of the gene. LOXL1 was found to be expressed by reverse transcription-polymerase chain reaction in all ocular tissues examined except retina. The presence of LOXL1 protein in ocular tissues of interest was demonstrated by western blotting. Specific bands of ~130 and 80 kDa, representing polymerized protein forms, were detected in the cornea, iris, ciliary body, lens capsule and optic nerve. The 42 kDa mature form of LOXL1 was detected in the iris and ciliary body. Our 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. This strongly suggests that as yet unidentified genetic or environmental factors independent of LOXL1 strongly influence the phenotypic expression of the syndrome.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:50093
Year Published:2008
Web of Science® Times Cited:120
Deposited By:Medicine
Deposited On:2008-06-10
Last Modified:2014-11-04

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