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试溶性ApoL1变种与非裔美国人的脏疾病的关联
Giulio Genovese1, David J Friedman, Michael D Ross
1Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
概括
两种APOL1基因变异与非洲裔美国人的病率更高有关. 这些在非洲常见的变种可能会对寄生虫提供保护,但会增加病风险.
科学领域:
- 遗传学 遗传学 是一个
- 腎臟病學 (nephrology) 是一種醫學專業.
- 进化生物学 进化生物学
背景情况:
- 与欧洲裔美国人相比,非洲裔美国人的病发病率不成比例地高.
- 焦点细分性淋巴细胞硬化 (FSGS) 和高血压归因于末期病 (H-ESKD) 是这种差异的重要贡献者.
研究的目的:
- 调查非裔美国人增加FSGS和H-ESKD风险的遗传基础.
- 为了识别与这些脏疾病相关的APOL1基因中的特定遗传变异.
主要方法:
- 在染色体22上的APOL1基因中对序列变异的分析.
- 案例控制关联研究以确定FSGS和H-ESKD的赔率比率.
- 哈普洛型分析以评估APOL1变种的进化史和分布.
- 在体外测试评估APOL1变体对Trypanosoma brucei rhodesiense的功能性质.
主要成果:
- 在非裔美国人中,APOL1基因的两个独立序列变异与FSGS (odds比率=10.5) 和H-ESKD (odds比率=7.3) 的风险增加有显著的关联.
- 这些APOL1变种在非洲人群中普遍存在,但在欧洲人群中不存在.
- 相关的APOL1变体位于表现出积极选择特征的单元型上.
- 实验室研究表明,只有病相关的ApoL1变种表现出解活性.
结论:
- 特定的APOL1基因变异与非洲裔美国人的焦点细分型血球样硬化和高血压归因于末期病有很强的关联.
- 进化选择APOL1变种,可能是为了保护非洲试虫病,可能无意中导致非洲血统人口对病的易感性增加.
- 这些发现突显了传染病耐药性和慢性病患病率之间的潜在遗传联系.
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