NOTCH3 gene polymorphism in Japanese stroke patients

日本脑卒中患者NOTCH3基因多态性

• 批准号: 11670635
• 负责人: MAKINO Masahiro
• 金额: $ 2.05万
• 依托单位: KYOTO Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670635/
• 关键词: NOTCH3; CADASIL; STROKE; CADASIL; Notch3; vascular dementia; lacunar infarction; Iacunar infarction

CADASIL is caused by a single mutation of NOTCH3 with substitution of amino acid. We tested a hypothesis that polymorphisms in NOTCH3 might modulate onset age of stroke or incidence of lacunae in sporadic cerebrovascular patients. Subjects were 111 sporadic stroke patients and 23 normal controls. Subtypes of stroke were lacunar infarction (L) (n=59), atherothrombotic infarction (AT) (n=33), and cardioembolic infarction (CE) (n=19). Incidences of T allele at 381 nucleotide of NOTCH3 in stroke patients and normal subjects were 32.6% and 33.3 %, respectively (x=0.01,p=0.92). T allele in each stroke subgroup was 40.7 % in L, 30.3 % in AT,15.8 % in CE, and 32.6 % in N, and these T allele frequencies were not different from control. Incidences of A allele at 684 nucleotide in stroke patients and normal subjects were 8.1 % and 6.5 %, respectively (x=0.13,p=0.72). Incidence of A allele in each stroke subtype did not significantly differ from control. Our results revealed that polymorphisms of NOTCH3 at exon3 and 4 was often detected in Japanese stoke patients as well as normal control, but no association was observed between NOTCH3 polymorphism and sporadic stroke in Japanese patients.

CADASIL是由NOTCH3氨基酸替代的单一突变引起的。我们验证了一种假设，即NOTCH3基因的多态可能调节散发性脑血管病人卒中的发病年龄或腔隙的发生率。研究对象为散发性卒中患者111例和正常对照组23例。卒中亚型为腔隙性脑梗塞(L)59例，动脉粥样硬化性脑梗塞(AT)33例，心栓性脑梗塞(CE)19例。NOTCH3基因第381位核苷酸T等位基因频率在卒中组和正常对照组分别为32.6%和33.3%(x=0.01，p=0.92)。各卒中亚组T等位基因频率分别为：L组40.7%、AT组30.3%、CE组15.8%、N组32.6%，与对照组比较差异无统计学意义。684位核苷酸A等位基因在卒中患者和正常人中的分布频率分别为8.1%和6.5%(x=0.13，p=0.72)。A等位基因在各卒中亚型中的发生率与对照组无显著差异。结果表明，NOTCH3基因外显子3和4的多态性在日本卒中患者和正常对照组中普遍存在，但在日本散发性卒中患者中未发现其与NOTCH3基因的关联。

项目成果

T Mizuno: "Lack of association between Notch3 gene polymorphism and cerebrovascular disease in Japanese sporadic stroke patients"Ann New York Acad Sci. 977. 252-257 (2002)

T Mizuno：“Notch3 基因多态性与日本散发性中风患者的脑血管疾病之间缺乏关联”Ann New York Acad Sci。

T Mizuno, M Makino, Y Fujiwara J Nagura, K Shiga, K Yoshikawa, K Nakajima, M Nakagawa: "Renin angiotensin system gene polymorphismin Japanese stroke patients."Molecular mechanism and epochal therapeutics of ischemic stroke and dementia (edited by Abe K.)

T Mizuno、M Makino、Y Fujiwara J Nagura、K Shiga、K Yoshikawa、K Nakajima、M Nakakawa：“日本中风患者的肾素血管紧张素系统基因多态性”。缺血性中风和痴呆的分子机制和划时代的治疗（Abe K.

T Mizuno: "Renin angiotensin system gene polymorphism in Japanese stroke patients."In "Molecular mechanism and epochal therapeutics of ischemic stroke and dementia" edited by Abe K. International Congress Series. 1252. 83-90 (2003)

T Mizuno：“日本中风患者的肾素血管紧张素系统基因多态性”。载于Abe K.国际大会系列编辑的“缺血性中风和痴呆的分子机制和划时代疗法”。

T Mizuno, M Makino, Y Fujiwara, K Nakajima: "Lack of association between Notch3 gene polymorphism and cerebrovascular disease in Japanese sporadic stroke patients"Ann New York Acad Sci. vol.977. 252-257 (2002)

T Mizuno、M Makino、Y Fujiwara、K Nakajima：“Notch3 基因多态性与日本散发性中风患者的脑血管疾病之间缺乏关联”Ann New York Acad Sci。