与内皮细胞相关的遗传变异识别了对LDL胆固醇敏感的个体,这些个体从积极的脂质降低中获得了更大的好处
Nicholas A Marston1,2, Frederick K Kamanu3,4, Giorgio E M Melloni3,4
1Division of Cardiology, TIMI Study Group, Boston, MA, USA. nmarston@bwh.harvard.edu.
对内皮细胞 (EC) 功能的新多基因风险评分 (PRS) 独立预测冠状动脉疾病 (CAD) 风险. 具有高ECPRS的个体从降低LDL-C的治疗中获益更多,以预防心血管疾病.
科学领域:
- 心血管遗传学 心血管遗传学
- 内皮细胞生物学 内皮细胞生物学
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 内皮细胞 (EC) 功能障碍与冠状动脉样硬化易感性有关.
- 在CAD风险中,EC功能和低密度脂蛋白胆固醇 (LDL-C) 之间的相互作用尚不清楚.
- 全基因组关联研究 (GWAS) 提供了对复杂疾病遗传倾向的见解.
研究的目的:
- 研究EC功能障碍在冠状动脉疾病 (CAD) 易感性中的作用.
- 开发和验证EC特定的多基因风险评分 (EC PRS) 用于CAD风险预测.
- 为了确定LDL-C度是否会改变EC PRS与心血管疾病 (CVD) 风险之间的关联.
主要方法:
- 从GWAS数据中确定了EC功能相关的单核酸多态 (SNP).
- 使用这些已识别的变体构建了一个35-SNP EC PRS.
- 在三个独立的队列中验证了EC PRS (英国生物银行,木星,Fourier),包括初级和二级预防人群.
主要成果:
- 独立地,EC PRS与整个队列中发生 CAD 的风险增加有关.
- 较低的LDL-C度显著改变了与EC PRS相关的风险;在较高的LDL-C度下,风险更高.
- 与EC PRS较低的人相比,高EC PRS的个体从降低LDL-C的疗法中显示出明显更大的相对风险降低.
结论:
- 欧共体PRS量化了CAD风险的独立轴,目前还没有在临床实践中进行评估.
- 欧共体PRS识别了对LDL-C的异位性影响更敏感的个体.
- 这些发现表明,EC PRS可以识别那些从积极的LDL-C降低策略中获得更大的好处的患者.
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