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Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
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阿波脂蛋白E和慢性病的进展.

Charles C Hsu1, W H Linda Kao, Josef Coresh

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概括

Apolipoprotein E (APOE) 的遗传变异影响慢性病 (CKD) 的进展. 不管其他因素如何,epsilon4等位基因降低了风险,而epsilon2则增加了风险. 这突显了CKD中的非脂质通路.

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科学领域:

  • 遗传学和基因组学 遗传学和基因组学
  • 腎臟病學 (nephrology) 是一種醫學專業.
  • 流行病学 流行病学

背景情况:

  • 阿波利波蛋白E (APOE) 的epsilon2等位基因与糖尿病脏病风险增加有关,而epsilon4与风险降低有关.
  • APOE与慢性病 (CKD) 进展超出糖尿病病的关联在很大程度上尚未研究,特别是在非洲裔美国人中.

研究的目的:

  • 确定与APOE基因型和等位基因相关的CKD进展风险.
  • 在一个多元的人群中调查这些关联,包括白人,非裔美国人,糖尿病人和非糖尿病人.

主要方法:

  • 从ARIC研究中对3859名非裔美国人和10,661名白人成年人 (年龄在45-64岁) 的前性随访.
  • 事件慢性病进展定义为住院治疗,死于病,或血清肌氨酸显著增加.
  • 分析APOE基因型和代基因与中位数14年的CKD进展关系.

主要成果:

  • APOE epsilon2 适度增加了CKD进展风险 (RR,1.08),而epsilon4 降低了这一风险 (RR,0.85),独立于主要风险因素和脂质.
  • APOE epsilon4显著降低了末期脏疾病的风险 (RR,0.60).
  • APOE epsilon2与功能下降有关 (RR,1.25) 但与住院治疗或ESRD等特定事件无关.
  • 这些关联在种族,性别,糖尿病和高血压方面都是一致的. 非洲裔美国人的CKD风险过高并不能由APOE等位基因解释.

结论:

  • APOE遗传变异是CKD进展的重要预测因素,独立于糖尿病,种族和脂质特征.
  • 研究结果表明,非脂质介导的途径,可能涉及脏重塑的细胞机制,有助于APOE在CKD进展中的作用.