| Project/Area Number |
15591552
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Tokyo Women's Medical University |
|---|
Principal Investigator |
KASUYA Hidetoshi (2004) Tokyo Women's Medical University, Assistant Professor, 医学部・脳神経外科, 講師 (50169455)
恩田 英明 (2003) 東京女子医科大学, 医学部, 助手 (60185692)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
INOUE Ituro Tokyo Women's Medical University, Associate Professor, 医科学研究所, 助教授 (00192500)
AIHARA Yasuo Tokyo Women's Medical University, Lecturer, 医学部, 助手 (50287372)
糟谷 英俊 東京女子医科大学, 医学部, 講師 (50169455)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
|
|---|
| Keywords | aneurysm / subarachnoid hemorrhage / susceptible gene / chromosome 7 / 遺伝解析 / エラスチン / ハプロタイプ |
|---|
| Research Abstract |
We previously performed a genome-wide linkage study of intracranial aneurysm(IA) and found significant linkage at chromosome 7q11(MLS=3.22 near D7S2472). In the present study, the linkage region was extensively studied through linkage disequilibrium(LD) mapping and haplotype analysis covering 4.7 Mb. 26 positional candidate genes lie in the region, and 168 gene-based single-nucleotide polymorphisms(SNPs) were genotyped. For systematic and comprehensive analysis of the linkage region, we performed sliding window analysis. The window, which contains 2〜4 adjacent SNPs, slid over the linkage region scanning LD structure and susceptible alleles for IA. Allelic association was assessed by permutation test, which adjusts the significance level to account for multiple comparisons in the data sets. Our sliding window analysis showed that the linkage region was mostly constructed by gene-specific LD blocks, and positive associations between IA were observed in one distinct LD block (P<0.01), in where 3' end of ELN and 5' regulatory region of LIMK1 genes were involved. The 2 genes were located _400 kb centromeric from D7S2472. Extensive association studies of the LD block indicated that the SNP in 3' untranslated region [+659] of ELN gene were strongly associated with IA (P=0.00006 in the dominant model), in 251 IA patients and 241 controls. Identification of the locus of susceptibility to IA by these systematic association studies permits us to investigate the pathogenesis of the disease.
|
