モヤモヤ病の遺伝子解析

烟雾病的遗传分析

• 批准号: 10470295
• 负责人: MATSUSHIMA toshio
• 金额: $ 7.49万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470295/
• 关键词: moyamoya disease; HLA; Genetic abnormality

1. Linkage studyIn the 19th families affected by moyamoya disease, blood samples was obtained from all members of the family. Microsatellite markers on the 6th chromosome were amplified by using polymerase chain reaction. Sharing of the allele was investigated among affected members, considering the haplotype. The marker, D6S441 had a possible linkage with moyamoya disease. Thus, around the D6S441, responsible gene for moyamoya disease might be located. Another institute analyzed and reported that chromosome 3 was linked to moyamoya disease. According to clinical genetics, moyamoya disease shows multifactorial inheritance. Further analysis might show other region linked to moyamoya disease.2. Polymorphisms of TGFB1 and TGFBR 2 genesRecent studies have shown increased production of serum transforming growth factor (TGF)βィイD21ィエD2 and its mRNA level from cultured smooth muscle cells in patients with Moyamoya disease. TGF-β signaling system has been suggested to be associated with the pathogenesis of Moyamoya disease. We analyzed the polymorphisms of TGFB1 and TGFBR 2 genes in 61 Moyamoya patients. Our study has shown that there were no associations between Moyamoya disease and polymorphisms of TGFB1/TGFBR 2 genes. Thus, it is likely that increases of TGFβ1 in serum and vascular smooth muscle cells were not primary but secondary events in Moyamoya disease.3. Renin-angiotensin systemThe plasma levels of renin, angiotensin I, and angiotensin II were investigated in 48 Moyamoya patients. The level of angiotensin I was markedly elevated in the patients. It was not clear whether this increase was primary or secondary. Further investigation is needed to clarify the fact.

1.关联研究在19个烟雾病家庭中，采集了所有家庭成员的血液样本。通过聚合酶链式反应扩增第 6 号染色体上的微卫星标记。考虑到单倍型，对受影响成员之间的等位基因共享进行了调查。标记物 D6S441 可能与烟雾病有关。因此，烟雾病的相关基因可能位于 D6S441 周围。另一家研究所分析并报告称，3 号染色体与烟雾病有关。根据临床遗传学，烟雾病表现出多因素遗传。进一步的分析可能会发现其他区域与烟雾病有关。2． TGFB1 和 TGFBR 2 基因的多态性最近的研究表明，烟雾病患者培养的平滑肌细胞中血清转化生长因子 (TGF)βiiD21iiD2 的产生及其 mRNA 水平增加。 TGF-β信号系统被认为与烟雾病的发病机制有关。我们分析了 61 名烟雾病患者的 TGFB1 和 TGFBR 2 基因多态性。我们的研究表明烟雾病与 TGFB1/TGFBR 2 基因多态性之间没有关联。因此，血清和血管平滑肌细胞中TGFβ1的增加很可能不是烟雾病的原发事件而是继发事件。3．肾素-血管紧张素系统对 48 名烟雾病患者的血浆肾素、血管紧张素 I 和血管紧张素 II 水平进行了研究。患者的血管紧张素I水平显着升高。目前尚不清楚这种增加是原发性的还是继发性的。还需要进一步调查来澄清事实。

项目成果

Ikezaki K et al: "Rational approach to treatment of moyamoya disease in childhood"J Child Neurology. 15 (in press).

Ikezaki K 等人：“儿童烟雾病的合理治疗方法”J Child Neurology。

Ueno M et al: "Moyamoya disease and Transforming Growth Factor-βィイD21ィエD2"Journal of neurosurgery. (in press).

Ueno M 等人：“烟雾病和转化生长因子-βD21D2”神经外科杂志（正在出版）。

Iwamatsu M et al: "Case report of Hirschsprung disease associated with occlusion of Willis arterial circle : Analysis of endothelin B receptor"Tokyo women's medical university. 69. 112-117 (1998)

Iwamatsu M等人：“与威利斯动脉环闭塞相关的先天性巨结肠病的病例报告：内皮素B受体的分析”东京女子医科大学。

Inoue TK et al: "Linkage analysis moyamoya disease on chromosome 6"Journal of child neurology. (in press).

Inoue TK等：“6号染色体上烟雾病的连锁分析”儿童神经病学杂志。

Yamauchi T et al: "Linkage of familial moyamoya disease (spontaneous occulusion of the circle of Willis) to chromosome 17q25"Stroke. (in press).

Yamauchi T 等人：“家族性烟雾病（威利斯环自发闭塞）与染色体 17q25 的关联”中风。