School of Rehabilitation, Capital Medical University, Beijing, China; Beijing Bo' ai Hospital, China Rehabilitation Research Center, Beijing, China.
Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, China.
J Stroke Cerebrovasc Dis. 2024 Dec;33(12):108039. doi: 10.1016/j.jstrokecerebrovasdis.2024.108039. Epub 2024 Sep 25.
Diet-derived circulating antioxidants have been associated with functional outcome after ischemic stroke (IS), but the causality remains unclear. The aim of our study is to explore the potential causal effect of diet-derived circulating antioxidants on long-term functional outcome (at 3 months) following IS through the utilization of the Mendelian randomization (MR) approach.
For this two-sample MR analysis, genetic variants associated with the diet-derived circulating antioxidants, including selenium, zinc, vitamin A (retinol), vitamin C, and vitamin E (α-tocopherol and γ-tocopherol), were identified in a large-scale Genome-Wide Association Studies (GWAS) database and utilized as instrumental variables (IVs). Summary data for long-term functional outcome after IS were obtained from the Genetics of Ischemic Stroke Functional Outcome (GISCOME) network of 6021 patients. Our study used the Inverse-variance weighting method as our primary MR method and also performed a series of sensitivity analyses for pleiotropy and heterogeneity.
We observed that selenium (odds ratio (OR)=0.81; 95 % confidence interval (CI): 0.68-0.97; p=0.02) was significantly associated with poor functional outcome (modified Rankin Scale score≥3) after IS. Genetic liabilities to other diet-derived circulating antioxidants were not strongly associated with functional outcome after IS (all p>0.05). Sensitivity analyses confirmed the reliability of these results.
This MR study suggested the positive effect of selenium on the long-term functional outcome after IS. Giving a longer period of selenium exposure can be used as a potential treatment to improve recovery after IS.
饮食来源的循环抗氧化剂与缺血性中风（IS）后的功能结果相关，但因果关系尚不清楚。我们的研究目的是通过利用孟德尔随机化（MR）方法来探索饮食来源的循环抗氧化剂对 IS 后长期功能结果（3 个月时）的潜在因果影响。
在这项两样本 MR 分析中，与饮食来源的循环抗氧化剂相关的遗传变异，包括硒、锌、维生素 A（视黄醇）、维生素 C 和维生素 E（α-生育酚和γ-生育酚），在一个大型全基因组关联研究（GWAS）数据库中被确定，并被用作工具变量（IVs）。来自 6021 例 IS 后长期功能结果的遗传学缺血性中风功能结果（GISCOME）网络获得了长期功能结果的汇总数据。我们的研究使用逆方差加权法作为主要的 MR 方法，并对多效性和异质性进行了一系列敏感性分析。
我们发现硒（比值比（OR）=0.81；95%置信区间（CI）：0.68-0.97；p=0.02）与 IS 后不良功能结果（改良 Rankin 量表评分≥3）显著相关。其他饮食来源的循环抗氧化剂的遗传易感性与 IS 后功能结果没有强烈关联（均 p>0.05）。敏感性分析证实了这些结果的可靠性。
这项 MR 研究表明，硒对 IS 后长期功能结果有积极影响。给予更长时间的硒暴露可以作为改善 IS 后恢复的潜在治疗方法。
