可溶性免疫检查点蛋白质和脂质网络与全因死亡风险的关联:精准医学的跨奥米学 (TOPMed) 计划
medRxiv : the preprint server for health sciences
|January 20, 2025
概括
免疫检查点疗法可能会增加心血管风险. 特定的血蛋白 LAG3 和 HAVCR2 与死亡率有关,与高密度胆固醇相关的遗传变异可能提供进一步的风险预测.
科学领域:
- 心血管疾病是什么心血管疾病
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 蛋白质组学是指蛋白质组学.
背景情况:
- 免疫检查点抑制剂 (ICI) 正在彻底改变癌症治疗.
- 心血管不良事件是ICI使用的一个新兴问题.
- 了解将ICI与心血管风险联系起来的分子机制至关重要.
研究的目的:
- 研究免疫检查点血蛋白与心血管风险因素之间的关联.
- 探索与高密度脂蛋白胆固醇 (HDL-C) 和低密度脂蛋白胆固醇 (LDL-C) 相关的蛋白质网络.
- 评估这些蛋白质网络与全因死亡风险的关联.
主要方法:
- 利用了Trans-Omics for Precision Medicine计划的数据集,包括动脉样硬化多民族研究,杰克逊心脏研究 (JHS) 和弗雷明翰心脏研究.
- 检查了免疫检查点血蛋白,HDL-C和LDL-C之间的关联.
- 通过使用全基因组关联研究 (GWAS) 对HDL-C/LDL-C和蛋白质定量特征位点 (pQTLs) 进行了局部化分析,来自JHS和社区中的动脉样硬化风险.
主要成果:
- 淋巴细胞激活基因3 (LAG3) 和甲型肝炎病毒细胞受体2 (HAVCR2) 的血水平与死亡风险显著相关.
- TFF3 rs60467699和CD36 rs3211938的变体显著地与HDL-C.有着共同的局部关系.
- 在遗传变异和LDL-C之间没有观察到任何显著的局部化.
结论:
- 血LAG3和HAVCR2水平与死亡风险增加有关.
- 与HDL-C相关的特定遗传变异可能导致心血管风险.
- 测量血LAG3,HAVCR2和相关蛋白质,以及针对性基因定型,可以帮助识别高风险患者.
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