Longitudinal study in an island community for aging effects on neurological findings and genetic factors on vascular dementia

在岛屿社区中进行的纵向研究，了解衰老对神经系统检查结果的影响以及血管性痴呆的遗传因素

• 批准号: 10670596
• 负责人: NAKAGAWA Masanori
• 金额: $ 1.86万
• 依托单位: Kagoshima University
• 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 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670596/
• 关键词: Aging effects on nervous system; Dementia; Genetic factors; Elders in an island community; Cerebrovascular disorders; MMSE; Polymorphism of ACE gene; Mitochondria DNA 5178; 脳血管性痴呆; 神経疾患

Purpose: To clarify aging effects on neurological findings and genetic factors related to vascular dementia, we analyzed neurological findings in elders living an island community and genetic factors in patients with cerebrovascular disorders (CVD).Methods and materials: 1) Neurological findings, dementia scale (MMSE) and dietary intake in the elders aged 60 year-old or over living in an island in Kagoshima, Japan were studied every other year. 2) Angiotensin converting enzyme (ACE) gene (II, ID, DD) and mitochondria 5178C/A polymorphism were analyzed in patients with CVD (127 cases) and the elders in an island (294 cases).Results: 1) The longitudinal study in the elders in an island. The score of MMSE in 590 elders was decreased with aging and the decrease ratio was higher in elders with aging. The incidence of cardiac disorders was significantly high in the elders without decrement of MMSE scale, but the incidence of renal disorders was high in the elders with decrement of the scale. Some dietary intake (tempura etc) showed negative correlation with MMSE score. 2) Genetic polymorphism and CVD. The mitochondrial DNA (mtDNA) polymorphism, 5178C, was significantly dominant in patients with CVD (p<0.01). MtDNA5178C was also dominant in all CVD subtypes without statistical difference between CVD subtypes. The women CVD patients with mt5178C showed higher total cholesterol and triglyceride levels in serum. ACE genotypes and allele frequency were not different between CVD patients and control or between CVD subtypes.Conclusions: In this study, we showed the longitudinal change of dementia scale and the factors that might be related to the change in elders living in an island. We also demonstrated the genetic factors that might be related to the onset of CVD.

目的：为探讨年龄对血管性痴呆的神经学表现和遗传因素的影响，我们分析了居住在海岛社区的老年人的神经学表现和脑血管疾病（CVD）患者的遗传因素。方法和材料：1）每隔一年研究一次居住在日本鹿儿岛的60岁以上老年人的神经学表现、痴呆量表（MMSE）和饮食摄入。2)对127例脑血管病患者和294例海岛老年人进行血管紧张素转换酶（ACE）基因（II、ID、DD）和线粒体5178 C/A多态性分析。590名老年人MMSE评分随增龄而下降，且随增龄下降比例更高。MMSE评分未降低的老年人心脏疾病的发生率明显高于MMSE评分降低的老年人，而肾脏疾病的发生率明显高于MMSE评分降低的老年人。某些饮食摄入（天妇罗等）与MMSE评分呈负相关。2)遗传多态性与CVD线粒体DNA（mtDNA）5178 C多态性在脑血管病患者中明显占优势（P<0.01）。MtDNA 5178 C在所有CVD亚型中也占优势，但CVD亚型之间无统计学差异。女性心血管病患者mt5178 C显示较高的血清总胆固醇和甘油三酯水平。ACE基因型和等位基因频率在CVD患者和对照组之间或CVD亚型之间没有差异。结论：在这项研究中，我们显示了痴呆量表的纵向变化和可能与居住在一个岛屿的老年人的变化有关的因素。我们还证实了可能与CVD发病有关的遗传因素。

项目成果

Isashiki Y, Nakagawa M, Ohba N, et al.: "Retinal manifestations in mitochondrial diseases associated with mitochondrial DNA mutation"Acta Ophthalmologica Scandinavica. 76. 6-13 (1998)

Isashiki Y、Nakakawa M、Ohba N 等人：“与线粒体 DNA 突变相关的线粒体疾病中的视网膜表现”Acta Olookingmologica Scandinavica。

Yamagata H, Nakagawa M, Johnson K, Miki T.: "Further evidence for a major ancient mutation underlying myotonic dystrophy from linkage disequilibrium studies in the Japanese population."Journal of Human Genetics. 43. 246-249 (1998)

Yamagata H、Nakakawa M、Johnson K、Miki T.：“从日本人群的连锁不平衡研究中进一步证明了强直性肌营养不良背后的主要古代突变。”人类遗传学杂志。

Takashima H, Nakagawa M, Suehara M, Saito M, Saito A, Kanzato N, Matsuzaki T,Hirata K, Terwilliger JD, Osame M.: "Gene for hereditary motor and sensory neuropathy (proximal dominant form) mapped to 3q13.1"Neuromuscular Disorders. 9. 368-371 (1999)

Takashima H, Nakakawa M, Suehara M, Saito M, Saito A, Kanzato N, Matsuzaki T,Hirata K, Terwilliger JD, Osame M.：“遗传性运动和感觉神经病（近端显性形式）映射到 3q13.1 的基因”

Nakagawa M, Suehara M, Saito A, et al.: "A novel MPZ gene mutation in dominantly inherited neuropathy with focally folded myelin sheaths"Neurology. 52. 1271-1275 (1999)

Nakakawa M、Suehara M、Saito A 等人：“局灶性折叠髓鞘显性遗传性神经病中的新型 MPZ 基因突变”神经病学。

Ohkubo R, Nakagawa M, Higuchi I, et al.: "familial skeletal myopathy with atrioventricular block"Internal medicine. 38. 856-860 (1999)

Ohkubo R，Nakakawa M，Higuchi I，等：“家族性骨骼肌病伴房室传导阻滞”内科。