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Originally published in Science Express on 9 August 2007
Science 7 September 2007:
Vol. 317. no. 5843, pp. 1397 - 1400
DOI: 10.1126/science.1146554
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Reports

Common Sequence Variants in the LOXL1 Gene Confer Susceptibility to Exfoliation Glaucoma

Gudmar Thorleifsson,1* Kristinn P. Magnusson,1* Patrick Sulem,1* G. Bragi Walters,1 Daniel F. Gudbjartsson,1 Hreinn Stefansson,1 Thorlakur Jonsson,1 Adalbjorg Jonasdottir,1 Aslaug Jonasdottir,1 Gerdur Stefansdottir,1 Gisli Masson,1 Gudmundur A. Hardarson,1 Hjorvar Petursson,1 Arsaell Arnarsson,2 Mehdi Motallebipour,3 Ola Wallerman,3 Claes Wadelius,3 Jeffrey R. Gulcher,1 Unnur Thorsteinsdottir,1 Augustine Kong,1 Fridbert Jonasson,2,4{dagger} Kari Stefansson1{dagger}

Glaucoma is a leading cause of irreversible blindness. A genome-wide search yielded multiple single-nucleotide polymorphisms (SNPs) in the 15q24.1 region associated with glaucoma. Further investigation revealed that the association is confined to exfoliation glaucoma (XFG). Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS). About 25% of the general population is homozygous for the highest-risk haplotype, and their risk of suffering from XFG is more than 100 times that of individuals carrying only low-risk haplotypes. The population-attributable risk is more than 99%. The product of LOXL1 catalyzes the formation of elastin fibers found to be a major component of the lesions in XFG.

1 deCODE genetics Inc, 101 Reykjavik, Iceland.
2 Medical Faculty, University of Iceland, 101 Reykjavik, Iceland.
3 Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden.
4 Department of Ophthalmology, National University Hospital, 101 Rykjavik, Iceland.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: fridbert{at}landspitali.is (F.J.); kstefans{at}decode.is (K.S.)

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