Science
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, Hjorvar Petursson, Arsaell Arnarsson, Mehdi Motallebipour, Ola Wallerman, Claes Wadelius, Jeffrey R. Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Fridbert Jonasson, Kari Stefansson
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.
Science. 2007;317(5843):1397-1400..