Artikel
Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11
Genlocus für intrakranielle Aneurysmen auf dem Chromosom 7q11
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Autoren
Veröffentlicht: | 23. April 2004 |
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Gliederung
Text
Objective
Rupture of intracranial aneurysms causes subarachnoid hemorrhage, a devastating condition with high morbidity and mortality. Angiographic and autopsy studies show that an intracranial aneurysm is a common disorder, with a prevalence of 3%-6%. Although it has a substantial genetic component, little attention has been given to the genetic determinants.
Methods
We report here a genomewide linkage study of intracranial aneurysms in 104 Japanese affected sib pairs in which positive evidence of linkage on chromosomes 5q22-31 (maximum LOD score [MLS] 2.24), 7q11 (MLS 3.22), and 14q22 (MLS 2.31) were found. A cohort of 100 Caucasian patients with intracranial aneurysms are currently being examined in the same fashion.
Results
The best evidence of linkage is detected at D7S2472, in the vicinity of the elastin gene (ELN), a candidate gene for intracranial aneurysms. Fourteen distinct single-nucleotide polymorphisms (SNPs) were identified in ELN, and no obvious allelic association between IA and each SNP was observed. The haplotype between the intron-20/intron-23 polymorphism of ELN is strongly associated with IA (P=3.81x10-6), and homozygous patients are at high risk (P=.002), with an odds ratio of 4.39.
Conclusions
These findings suggest that a genetic locus for IA lies within or close to the ELN locus on chromosome 7 in a cohort of Japanese patients.