Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma.
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.
Thorleifsson
Gudmar
G
deCODE genetics Inc, 101 Reykjavik, Iceland.
Magnusson
Kristinn P
KP
Sulem
Patrick
P
Walters
G Bragi
GB
Gudbjartsson
Daniel F
DF
Stefansson
Hreinn
H
Jonsson
Thorlakur
T
Jonasdottir
Adalbjorg
A
Jonasdottir
Aslaug
A
Stefansdottir
Gerdur
G
Masson
Gisli
G
Hardarson
Gudmundur A
GA
Petursson
Hjorvar
H
Arnarsson
Arsaell
A
Motallebipour
Mehdi
M
Wallerman
Ola
O
Wadelius
Claes
C
Gulcher
Jeffrey R
JR
Thorsteinsdottir
Unnur
U
Kong
Augustine
A
Jonasson
Fridbert
F
Stefansson
Kari
K
D000273:Adipose Tissue / Q000378:metabolism; D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D017889:Exfoliation Syndrome / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005901:Glaucoma / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006801:Humans; D007055:Iceland; D008297:Male; D020641:Polymorphism, Single Nucleotide
D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human