不确定潜力 (CHIP) 和事件类型2型糖尿病风险的克隆性血液形成
Deirdre K Tobias1,2, Alisa K Manning3,4,5, Jennifer Wessel6
1Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Diabetes care
|September 27, 2023
概括
不确定潜力的克隆性血液形成 (CHIP) 增加了2型糖尿病的风险. 这种与衰老相关的疾病涉及血液干细胞的突变,突出显示了与心血管疾病的共同途径.
科学领域:
- 遗传学 遗传学 是一个
- 老年学是一门学科.
- 内分泌学 在内分泌学.
背景情况:
- 不确定潜力的克隆造血 (CHIP) 是一种与衰老相关的疾病,涉及血液造血干细胞的体质突变.
- CHIP与心血管疾病和死亡率有关,但其与发生型2型糖尿病 (T2D) 的关联尚不清楚.
研究的目的:
- 调查CHIP与发生2型糖尿病的风险之间的关联.
- 确定特定的CHIP相关基因突变 (DNMT3A,TET2,ASXL1,JAK2,TP53) 是否与T2D风险相关.
主要方法:
- 分析了TOPMed潜在队列中的17637名参与者的全基因组测序数据.
- 评估了基线CHIP状态,并在平均9.8年的随访期间跟踪T2D事件.
- 计算了多变量危险比率,调整了人口统计和生活方式因素,并对组合队列估计进行了元分析.
主要成果:
- 在没有T2D,心血管疾病或癌症的参与者中,CHIP患病率在基线为6.0%.
- 与没有CHIP的人相比,CHIP患者患T2D的风险高出23%.
- TET2和ASXL1基因的突变与T2D的风险增加有显著的关联.
结论:
- CHIP与较高的2型糖尿病发病率有关.
- CHIP突变与T2D之间的联系表明共享了与衰老相关的潜在生物途径.
- 进一步的研究可能会阐明连接CHIP和T2D病变的确切机制.
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