Diet-derived circulating antioxidants and functional outcome after ischemic stroke: Evidence from genetic studies

Objective

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.

Materials and methods

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.

Results

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.

Conclusion

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.