Filimonov Dmitry A, Morozov Vitaly V, Ishchenko Roman V, Eresko Alexander B, Trubnikova Nadezhda N, Belotserkovskaya Margarita A, Solopov Maksim V, Kisilenko Irina A, Nosova Inna N, Kudlay Dmitry A
Federal State Budgetary Institution "V.K. Gusak Institute of Emergency and Reconstructive Surgery" of the Ministry of Health of the Russian Federation, Donetsk 283045, Russia.
The Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Science, Novosibirsk 630090, Russia.
Life (Basel). 2025 Aug 16;15(8):1303. doi: 10.3390/life15081303.
The global burden of ischemic stroke requires a search for new factors that affect its risk and outcomes. Recent studies have shown that triiodothyronine could potentiate favorable stroke outcomes, but the reason for this is still unclear. To clarify the effects of the free triiodothyronine (fT3) level on stroke outcomes, we adopted a Mendelian randomization (MR) approach to evaluate their causal relationship. The genetic variants associated with the free triiodothyronine (fT3) level were obtained from the ThyroidOmics Consortium. Thirteen single-nucleotide polymorphisms, genetically predicting the fT3 level with a significance of < 10, were adopted for MR analysis. Summary-level data for ischemic stroke outcomes (reported as a continuous variable, namely the modified Rankin score 3 months after stroke) was obtained from the GISCOME network. MR analyses were performed using the TwoSampleMR framework. The inverse-variance weighting method of MR analysis showed that a genetically predicted increase in fT3 level is associated with a reduction in ordinal Modified Rankin Scale scores (OR = 0.581, 95% CI 0.37-0.92, = 0.0183). This study showed that higher fT3 levels could be causally associated with more favorable ischemic stroke outcomes and provides more evidence for the possibility of using thyroid hormone (TH) analogs to improve stroke outcomes.
缺血性中风的全球负担促使人们寻找影响其风险和预后的新因素。最近的研究表明，三碘甲状腺原氨酸可增强中风的良好预后，但原因尚不清楚。为了阐明游离三碘甲状腺原氨酸（fT3）水平对中风预后的影响，我们采用孟德尔随机化（MR）方法来评估它们之间的因果关系。与游离三碘甲状腺原氨酸（fT3）水平相关的基因变异来自甲状腺组学联盟。采用13个单核苷酸多态性进行MR分析，这些多态性在基因上预测fT3水平，显著性<10。缺血性中风预后的汇总数据（报告为连续变量，即中风后3个月的改良Rankin评分）来自GISCOME网络。使用TwoSampleMR框架进行MR分析。MR分析的逆方差加权法表明，基因预测的fT3水平升高与改良Rankin量表评分的降低相关（OR = 0.581，95% CI 0.37 - 0.92，P = 0.0183）。这项研究表明，较高的fT3水平可能与更良好的缺血性中风预后存在因果关系，并为使用甲状腺激素（TH）类似物改善中风预后的可能性提供了更多证据。
