Mutations in the lysyl oxidase gene not associated with intracranial aneurysm in central European families.
BACKGROUND
Lysyl oxidase is a promising candidate gene for a mutation search in intracranial aneurysm families because (a) it controls the processing, cross-linking and maturation of collagen and elastin fibers in the blood vessel wall, (b) its expression levels and activity are altered in different animal models of aneurysm pathogenesis, and (c) it is encoded within the chromosome 5q22-31 region of suggestive linkage to intracranial aneurysms.


METHODS
We have performed genomic sequencing of all 7 exons including the intron-exon splice sites and of the putative promoter region for lysyl oxidase in 25 patients from intracranial aneurysm multiplex families resident in Central Europe.


RESULTS
We observed 4 genetic variants including 2 novel polymorphisms, 1 in the noncoding sequence of exon 7 and the other upstream from the lysyl oxidase promoter. None of these single nucleotide polymorphisms showed an allelic association or cosegregation with intracranial aneurysm in the families.


CONCLUSIONS
Genetic variants in the lysyl oxidase gene do not appear to be a major factor in the etiology of intracranial aneurysms in Central Europe.
Clinic for Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Anne
A
Hofer
Süheyla
S
Ozkan
Marcella
M
Hermans
Nina
N
Kubassek
Matthias
M
Sitzer
Johannes
J
Burtscher
Ulrich
U
Knopp
Beate
B
Schoch
Isabel
I
Wanke
Felix
F
Huebner
Andreas
A
Raabe
Helmuth
H
Steinmetz
Georg
G
Auburger
D000225:Adenine; D000328:Adult; D000368:Aged; D001483:Base Sequence; D005060:Europe; D005260:Female; D014644:Genetic Variation; D006147:Guanine; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics*
D006147:Guanine; D008249:Protein-Lysine 6-Oxidase; D000225:Adenine