多基因评分对进展的贡献 在多发性硬化症中独立于复发活动的进展
Ferdinando Clarelli1, Melissa Sorosina1, Antonino Giordano1,2,3
1IRCCS San Raffaele Scientific Institute, Division of Neuroscience, Institute of Experimental Neurology, Laboratory of Human Genetics of Neurological Disorders, Milan, Italy.
European journal of neurology
|June 30, 2025
概括
遗传因素影响了多发性硬化症 (MS) 的残疾进展. 多基因风险评分 (PRS) 与不依赖复发活动 (PIRA) 事件的进展有关,特别是在年轻的MS患者中.
科学领域:
- 神经免疫学 神经免疫学
- 神经系统疾病的遗传学
- 多发性硬化症的发病因子
背景情况:
- 多发性硬化症 (MS) 患者经常经历独立于复发活动 (PIRA) 的残疾累积,甚至在疾病的早期.
- 了解PIRA的遗传贡献对于预测疾病轨迹和开发向疗法至关重要.
- 这项研究调查了PIRA在意大利MS患者队列中的遗传基础.
研究的目的:
- 评估在多发性硬化症 (MS) 中对进展独立于复发活动 (PIRA) 的遗传贡献.
- 评估多基因风险评分 (PRS) 与PIRA事件发生率之间的关联.
- 探索在MS残疾进展中遗传风险和发病时的年龄 (AAO) 之间的潜在相互作用.
主要方法:
- 多基因风险评分 (PRS) 来自一项关于多发性硬化症严重程度的大型全基因组关联研究 (>20,000名患者).
- 在采用聚合程序后,PRS在五个p值值下计算.
- 使用负二项回归模型来测试PRS与PIRA事件发生率之间的关联.
主要成果:
- 在整个队列中观察到PRS和PIRA事件发生率之间的关联趋势.
- 这种关联在患病发病年龄 (AAO) ≤50岁的患者中是显著的 (比率比率 = 1.148,p = 0.0328).
- 在PRS和AAO之间确定了显著的轻度对抗性相互作用效应 (p = 0.033).
结论:
- 遗传因素,特别是与严重程度相关的遗传负荷,似乎影响了MS中PIRA事件的发生率.
- 遗传风险对PIRA的影响在早期发病 (≤50岁) 的人群中更为明显.
- 研究结果表明,遗传风险评分对MS残疾累积的影响与年龄有关,这可能是由于年轻患者的衰老效应不那么突出.
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