Skip Navigation



Human Molecular Genetics Advance Access published online on April 12, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl096
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
15/10/1722    most recent
ddl096v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Akagawa, H.
Right arrow Articles by Inoue, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Akagawa, H.
Right arrow Articles by Inoue, I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org
Received February 20, 2006
Revised March 31, 2006
Accepted March 31, 2006

Article

A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms

Hiroyuki Akagawa 1, Atsushi Tajima 1, Yoshiko Sakamoto 1, Boris Krischek 1, Taku Yoneyama 1, Hidetoshi Kasuya 2, Hideaki Onda 2, Tomokatsu Hori 2, Motoo Kubota 3, Toshio Machida 3, Naokatsu Saeki 3, Akira Hata 4, Kazunari Hashiguchi 5, Eizou Kimura 5, Chul-Jin Kim 6, Tae-Ki Yang 6, Jong-Young Lee 7, Kuchan Kimm 7, and Ituro Inoue 8 *

1 Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
2 Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Tokyo, Japan
3 Department of Neurosurgery, School of Medicine, Chiba University, Chiba, Japan
4 Department of Public Health, School of Medicine, Chiba University, Chiba, Japan
5 Kousei General Hospital, Tokyo, Japan
6 Department of Neurosurgery, Chonbuk National University, Chonju, Korea
7 Center for Genome Science, National Institute of Health, Seoul, Korea
8 Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Japan

* To whom correspondence should be addressed.
Ituro Inoue, E-mail: ituro{at}ims.u-tokyo.ac.jp


  Abstract

The rupture of an intracranial aneurysm (IA) results in subarachnoid hemorrhage, a catastrophic neurological condition with high morbidity and mortality. Following up on our previous genome-wide linkage study in Japanese population, we extensively analyzed a 4.6 Mb linkage region around D7S2472 on 7q11 by genotyping 168 SNPs. SNP association and window scan haplotype-based association studies revealed a susceptibility locus for IA on a single LD block covering the 3'UTR of ELN and the entire region of LIMK1. An association study with 404 IA patients and 458 non-IA controls revealed that the ELN 3'UTR G(+659)C SNP has the strongest association to IA (P=0.000002) and constitutes a tag-SNP for an at-risk haplotype, which contains two functional SNPs, the ELN 3'UTR (+502) A insertion and the LIMK1 promoter C(-187)T SNP. These allelic and haplotype-based associations were confirmed in a Korean population. Ex vivo and in vitro analysis demonstrates that the functional impact of both SNPs is the decrease of transcript levels, either through accelerated ELN mRNA degradation or decreased LIMK1promoter activity. Elastin and LIMK1 protein are involved in the same actin depolymerization signaling pathway, therefore, these lines of evidence suggest a combined effect of the SNPs in the at-risk haplotype possibly by weakening the vascular wall and promoting the development of IA.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 StrokeHome page
Y. Yamada, N. Metoki, H. Yoshida, K. Satoh, K. Kato, T. Hibino, K. Yokoi, S. Watanabe, S. Ichihara, Y. Aoyagi, et al.
Genetic Factors for Ischemic and Hemorrhagic Stroke in Japanese Individuals
Stroke, August 1, 2008; 39(8): 2211 - 2218.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
T. Foroud, L. Sauerbeck, R. Brown, C. Anderson, D. Woo, D. Kleindorfer, M. L. Flaherty, R. Deka, R. Hornung, I. Meissner, et al.
Genome Screen to Detect Linkage to Intracranial Aneurysm Susceptibility Genes: The Familial Intracranial Aneurysm (FIA) Study
Stroke, May 1, 2008; 39(5): 1434 - 1440.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
N. Kondo, S. Honda, K. Ishibashi, Y. Tsukahara, and A. Negi
Elastin Gene Polymorphisms in Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy
Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 1101 - 1105.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
Y. M. Ruigrok and G. J.E. Rinkel
Genetics of Intracranial Aneurysms
Stroke, March 1, 2008; 39(3): 1049 - 1055.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. K. Ellis, Z. Z. Zhao, H.-G. Chen, G. W. Montgomery, Y.-S. Li, and D. P. McManus
Analysis of the 5q31 33 Locus Shows an Association between Single Nucleotide Polymorphism Variants in the IL-5 Gene and Symptomatic Infection with the Human Blood Fluke, Schistosoma japonicum
J. Immunol., December 15, 2007; 179(12): 8366 - 8371.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
S. Weinsheimer, K. A.B. Goddard, A. R. Parrado, Q. Lu, M. Sinha, E. R. Lebedeva, A. Ronkainen, M. Niemela, E. K. Khusnutdinova, R. I. Khusainova, et al.
Association of Kallikrein Gene Polymorphisms With Intracranial Aneurysms
Stroke, October 1, 2007; 38(10): 2670 - 2676.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
M. Dichgans and R. A. Hegele
Update on the Genetics of Stroke and Cerebrovascular Disease 2006
Stroke, February 1, 2007; 38(2): 216 - 218.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.