Key result
Genetically predicted higher neurotrophin-3 is linked to ~54% lower risk of hypertensive encephalopathy.
Why the study?
To investigate whether genetically predicted levels of five circulating cytokines are causally related to the risk of hypertensive encephalopathy.
Do genetically predicted levels of circulating cytokines (CXCL11, IL-2, IL-4, LIF, NT-3) alter the risk of developing hypertensive encephalopathy?
Observational (n=374,729)
Do genetically predicted levels of circulating cytokines (CXCL11, IL-2, IL-4, LIF, NT-3) alter the risk of developing hypertensive encephalopathy?
Odds Ratio: 0.46 (95% CI 0.28–0.75)
p-value: p=0.0038
This Mendelian randomization study provides novel genetic evidence that lifelong higher levels of IL-2, IL-4, and NT-3 may protect against hypertensive encephalopathy, while CXCL11 increases risk, highlighting potential immunomodulatory targets for severe hypertension complications.
Suggests NT-3, IL-4, and IL-2 as protective and CXCL11 as a risk factor for hypertensive encephalopathy; leaves open whether cytokine modulation improves outcomes.
Objectives: To investigate the causal relationship between genetically predicted levels of five circulating cytokines - CXCL11, IL-2, IL-4, leukemia inhibitory factor (LIF), and neurotrophin-3 (NT-3) - and the risk of hypertensive encephalopathy using a two-sample Mendelian randomization (MR) approach. Methods: ) were selected from publicly available GWAS data. Summary statistics for HE were obtained from the FinnGen biobank (endpoint: I9_HYPERTENC). MR analyses were conducted using inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses included heterogeneity testing, MR-Egger intercept assessment, and leave-one-out analysis. Results: 0.060). Results were consistent across sensitivity analyses with no evidence of pleiotropy or heterogeneity. Conclusions: This Mendelian randomization study provides evidence that genetically determined levels of IL-2, IL-4, and NT-3 are protective against hypertensive encephalopathy, while CXCL11 is a risk factor. These cytokines may serve as potential biomarkers or therapeutic targets for HE.
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Zhang et al. (2026) conducted an observational in Hypertensive encephalopathy (n=374,729). Genetically predicted higher levels of circulating cytokines (including NT-3, IL-2, IL-4, and CXCL11) vs. Unexposed/lower genetically predicted cytokine levels was evaluated on Risk of hypertensive encephalopathy (associated with Neurotrophin-3) (OR 0.46, 95% CI 0.28-0.75, p=0.0038). Genetically predicted higher levels of Neurotrophin-3 significantly decreased the risk of hypertensive encephalopathy (OR 0.46), with similar protective effects observed for IL-4 and IL-2, whereas higher CXCL11 increased the risk.
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