Please Note:

The Open Access Repository will be moving to a new authentication system on the 1st of November.

From this date onwards, account holders will be required to login using their University of Tasmania credentials.
If your current repository username differs from your University username, please email so we can update these details on your behalf.

Due to the change, there will be a short outage of the repository from 9am on the morning of the 1st of November

Open Access Repository

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


Downloads per month over past year

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 (2007) 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

[img] PDF
4412.pdf | Request a copy
Full text restricted


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 singlenucleotide
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 Type: Article
Journal or Publication Title: Human Molecular Genetics
Page Range: pp. 710-716
ISSN: 0964-6906
Identification Number - DOI: 10.1093/hmg/ddm342
Additional Information:

The definitive publisher-authenticated version

Date Deposited: 07 Apr 2008 14:38
Last Modified: 18 Nov 2014 03:35
Item Statistics: View statistics for this item

Actions (login required)

Item Control Page Item Control Page