Li Zhiguang, Li Yan, Zhao Jiankai, Zhang Feifei, Dang Wei, Jia Yanan, Guo Fei, Guo Lixin
Xingtai Central Hospital, Department of Neurology, Xingtai Hebei, People's Republic of China.
Xingtai Medical College, Department of Basic Medicine, Xingtai Hebei, People's Republic of China.
Arq Neuropsiquiatr. 2025 May;83(5):1-8. doi: 10.1055/s-0045-1804922. Epub 2025 May 13.
Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. The impacts of antihypertensive drugs and blood pressure (BP) on ALS are currently debatable.
To evaluate the causal relationship involving antihypertensive drugs, BP, and ALS through a Mendelian randomization (MR) analysis.
The causal relationship between BP and ALS was evaluated by a bidirectional two-sample MR analysis. Then, a sensitivity analysis was performed using a secondary BP genome-wide association study. The drug-target MR was employed to evaluate the impact of antihypertensive drugs on ALS. Furthermore, we used cis-expression quantitative trait loci (cis-eQTLs) data from brain tissue and blood to validate the positive results by a summary-based MR method.
We found that an increment in systolic BP (SBP) could elevate the risk of ALS (inverse-variance weighted [IVW] odds ratio [OR] = 1.003; 95% confidence interval [95%CI]: 1.001-1.006; per 10-mmHg increment) and ALS might be protected by angiotensin-converting enzyme inhibitors (ACEIs; OR = 0.970; 95%CI: 0.956-0.984; = 1.96 × 10; per 10-mmHg decrement). A causal relationship was not observed between diastolic BP and other antihypertensive drugs in ALS.
In the present study, genetic support for elevated SBP serves as a risk factor for ALS. Besides, ACEIs hold promise as a candidate for ALS.
肌萎缩侧索硬化症（ALS）是一种致命且无法治愈的神经退行性疾病。目前，降压药物和血压（BP）对ALS的影响存在争议。
通过孟德尔随机化（MR）分析评估降压药物、血压与ALS之间的因果关系。
采用双向双样本MR分析评估血压与ALS之间的因果关系。然后，使用二次血压全基因组关联研究进行敏感性分析。采用药物靶点MR评估降压药物对ALS的影响。此外，我们使用来自脑组织和血液的顺式表达定量性状位点（cis-eQTL）数据，通过基于汇总的MR方法验证阳性结果。
我们发现收缩压（SBP）升高会增加患ALS的风险（逆方差加权[IVW]比值比[OR]=1.003；95%置信区间[95%CI]：1.001-1.006；每增加10 mmHg），而血管紧张素转换酶抑制剂（ACEIs）可能对ALS有保护作用（OR=0.970；95%CI：0.956-0.984；=1.96×10；每降低10 mmHg）。未观察到舒张压与ALS中其他降压药物之间存在因果关系。
在本研究中，收缩压升高作为ALS危险因素的遗传学证据得到支持。此外，ACEIs有望成为ALS的候选药物。
