Gene diagnoics of Sudden death and its practise

猝死的基因诊断及其实践

• 批准号: 10357004
• 负责人: TOYO-OKA Teruhiko
• 金额: $ 11.78万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10357004/
• 关键词: Gene; Diagnosis; Sudden death; Mitochondria; HCM; DCM; MELAS; D-loop; 遺伝子; Dループ; 発症前診断; 予防医学

Upto last year, we have reported gene analysis of mitochondrial DNA (mtDNA) mutation. This year, we analyzed evolutional modification of the gene mutation with special reference to cardiomyopathy development. Following the routine methods of gene isolation and preparation of mtDNA from patients with HCM, DCM, other cardiac diseases and normal control subjects, In the present study, we added the gene analysis of D-loop to characterize genetic lineage of the patients after PCR amplification.In summary, 162 cases with cardiomyopathy (HCM, 112 and DCM, 50 cases), we identified MELAS type mutation, i.e, A3243G, in 4 cases (2.5%) but found no case in 168 subjects without the cardiomyopathies. After analyzing 4 cases with MELAS-type mutation, to our surprise, 10 cases with other type cardiomyopathies and 23 subjects without cardiomyopathy, we found all subjects with these MELAS mutation segregated to one family with the common D-loop (Shin et al, Am.J.Hum.Genet.200Q). Accordingly, these results suggest the common roots of MELAS patients.

到去年为止，我们已经报道了线粒体DNA(MtDNA)突变的基因分析。今年，我们分析了基因突变的进化修饰，特别是与心肌病的发展有关。在本研究中，我们采用常规的基因分离和mtDNA制备方法，从肥厚型心肌病、扩张型心肌病、其他心脏病患者和正常对照人群中提取mtDNA，通过聚合酶链式反应分析，发现162例心肌病患者(肥厚型心肌病112例，扩张型心肌病50例)中有4例(2.5%)存在MELAS型突变，即A3243G，而在168例非心肌病患者中未发现该突变。在分析了4例MELAS型突变后，令我们惊讶的是，10例其他类型心肌病患者和23例非心肌病患者，我们发现所有携带这些MELAS突变的患者都被分离到一个具有共同D-loop的家族(Shin等，Am.J.Hum.Genet.200Q)。因此，这些结果提示了MELAS患者的共同根源。

项目成果

Shin WS, Toyo-oka T.: "Coculture of endothelial cells and vascular smooth muscle cells."Humana Press (London).

Shin WS，Toyo-oka T.：“内皮细胞和血管平滑肌细胞的共培养。”Humana Press（伦敦）。

Xi H et al.,: "Dystrophin disruption might be related to......"J.Cardiovasc.Pharmacol.. 36. S25-S29 (2000)

Xi H 等人：“肌营养不良蛋白破坏可能与……有关”J.Cardiovasc.Pharmacol.. 36. S25-S29 (2000)

Toyo-oka T.: "Long-and short-term cross talk between endothelial cells and vascular smooth muscle cells mediated by nitric oxide"Jpn. Heart J. 2001. (In press).

Toyo-oka T.：“一氧化氮介导的内皮细胞和血管平滑肌细胞之间的长期和短期串扰”Jpn。

Hikiji H et al.,: "Peroxynitrite production by TNF-α and IL-1β."Am.J.Physiol.. 278. E1031-E1037 (2000)

Hikiji H 等人，：“TNF-α 和 IL-1β 产生过氧亚硝酸盐。”Am.J.Physiol.. 278. E1031-E1037 (2000)

Wang Y., Chen J., Wang Y., et al.: "Crucial role of type 1, but not type 3, inositol 1,4,5-trisphosphate IP_3 receptors in IP_3-induced Ca^<2+> release, capacitative Ca^<2+> entry, and proliferation of A7r5 vascular smooth muscle cells"Circ. Res.. 88. 202

Wang Y.、Chen J.、Wang Y. 等人：“1 型（而非 3 型）肌醇 1,4,5-三磷酸 IP_3 受体在 IP_3 诱导的 Ca^2 > 释放、电容性