Genetic dissection of familial intracranial aneurysms by family-based approach

基于家庭的方法对家族性颅内动脉瘤进行基因解剖

• 批准号: 14207016
• 负责人: KOIZUMI Akio
• 金额: $ 29.04万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14207016/
• 关键词: Intracranial aneurysm; Genome-wide analysis; Genetic susceptibility; Linkage analysis; Association study; Chromosome 17; Family-based study; くも膜下出血; 家系; 遺伝子; ApoE; 家族性; 遺伝子解析; 多発家族; MRI; SNPs; リスク要因

In the study from 2002 to 2004, we have investigated 5 projects. First, we had recruited a study cohort of patients with familial histories of intracranial aneurysms (IA). Second, we conducted linkage analysis in these pedigrees. Third, we recruited cases and controls for the association study. Fourth, we conducted a replicating study for genes reported to be associated with IAs. Finally, we have tested whether a candidate gene found in pedigree study is associated with IA by a case-control study.1. A study cohort of pedigrees with familial IA : 29 families were recruited. From these families, 169 members took MRA screening. In these families, 104 members were found to have IA. Totally 273 members joined this study.2. Linkage analysis : We have conducted a linkage analysis for 29 families. The result revealed three significant regions : 17cent,19q13,and Xp22.3. A population for case-control study. Cases were defined as those who have been found to have IA by MRA/MRI or 3DCT angiography or angiography or been found to have IA by surgery for SAH. Controls were defined as those who were not having IA by MRA/MRI, are older than 40 years and are without family histories or histories of cerebrovascular diseases. Finally, we recruited 362 members and 332 members for cases and controls, respectively.4. A replication study : We have tested whether genes previously reported could be replicated or not. We selected Elastin (7q11), NOS2A(17cent), APOE (19q13) and ACE2(Xp22). We failed to replicate none of these genes in our population.5. Genes on 17cent : There are 108 genes on the linked region of chromosome 17cent. We selected 9 genes (TNFRSF13,M-RIP, COPS3,RAI1,SREBF1,GRAP MAPK7,MFPK7 and AKAP10) from this region. We conducted family study and case control studies'. A significant linkage and association was confirmed for TNFRSF13B.

在2002-2004年的研究中，我们调查了5个项目。首先，我们招募了一组有颅内动脉瘤(IA)家族史的患者进行研究。其次，对这些家系进行了连锁分析。第三，我们为关联研究招募了病例和对照。第四，我们对被报道与IAS相关的基因进行了重复研究。最后，我们通过病例对照研究验证了家系研究中发现的候选基因是否与IA有关。家族性IA家系队列研究：纳入29个家系。从这些家庭中，169名成员接受了MRA筛查。在这些家庭中，104名成员被发现患有IA。共有273名成员参加了这项研究。连锁分析：我们对29个家系进行了连锁分析。结果显示有三个显著区域：17cent、19q13和Xp22.3。病例对照研究的人群。病例定义为经MRA/MRI或3DCT血管造影或血管造影术发现或经手术证实的蛛网膜下腔出血患者。对照组被定义为经MRA/MRI检查无IA、年龄>40岁、无家族史或脑血管病史的患者。最后，我们招募了362名病例组成员和332名对照组成员。复制研究：我们已经测试了之前报道的基因是否可以复制。我们选择了弹性蛋白(7q11)、NOS2A(17美分)、APOE(19q13)和ACE2(Xp22)。我们没有在我们的种群中复制这些基因。17分上的基因：染色体17分上的连接区有108个基因。我们从该区域选择了9个基因(TNFRSF13、M-RIP、COPS3、RAI1、SREBF1、GRAP MAPK7、MFPK7和AKAP10)。我们进行了家庭研究和病例对照研究。证实了TNFRSF13B的显著连锁和关联。

项目成果

Evaluation of a Mass Screening Program for Lysinuric Protein Intolerance in the Northern Part of Japan

日本北部赖氨酸尿蛋白不耐受大规模筛查计划的评估

• 发表时间: 2003
• 期刊: Genetic Testing 7
• 作者: A.K.Dutta;Y.Okada;R.Z.Sabirov;Koizumi A. et al.
• 通讯作者: Koizumi A. et al.

Strategy of genetic analysis Basic Genetics in Medicine

遗传分析策略 医学基础遗传学

• 发表时间: 2003
• 作者: Maruyama;A.;Rusuwa;B.;Yuma;M.;Fukuta K. et al.;Inoue Y. et al.
• 通讯作者: Inoue Y. et al.

Inoue et al.: "Mutation Analysis of PKD1 in Japanese Autosomal Dominant Polycystic Kidney Disease (ADPKD)Patients"Human mutation. 19. 622-628 (2002)

Inoue等人：“日本常染色体显性多囊肾病（ADPKD）患者中PKD1的突变分析”人类突变。

脳神経外科疾患の責任遺伝子解析の概説

神经外科疾病的遗传分析概述

• 发表时间: 2004
• 期刊: 脳神経外科 32
• 作者: Yamada S;et al.;小泉昭夫他
• 通讯作者: 小泉昭夫他

家族性脳動脈奇形の遺伝子解析

家族性脑动脉畸形的遗传分析

• 发表时间: 2004
• 期刊: 脳神経外科ジャーナル別冊 13
• 作者: Miyoshi K;Asanuma M;Miyazaki I;Diaz-Corrales F.J.;Katayama T;Tohyama M.;Yamada et al.;小泉 昭夫 外;竹中 勝信 外
• 通讯作者: 竹中 勝信 外