• Postgrad Med J · Nov 2023

    Circulating sex hormone-binding globulin levels and ischemic stroke risk: a Mendelian randomization study.

    • Youjie Zeng, Si Cao, and Heng Yang.
    • Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
    • Postgrad Med J. 2023 Nov 20; 99 (1178): 127212791272-1279.

    PurposePrevious studies have presented conflicting findings regarding the protective effects of circulating sex hormone-binding globulin (SHBG) on ischemic stroke (IS). This study aimed to assess the causal effect of SHBG on IS using Mendelian randomization (MR) analysis and to identify potential mediators.MethodsFirst, the causal effect of SHBG on any IS (AIS), cardioembolic stroke (CES), large artery stroke (LAS), and small vessel stroke (SVS) was assessed by inverse variance weighed (IVW) method. Two additional MR methods (weighted median and MR-Egger) were used to supplement the IVW results. Subsequently, a two-step MR was further performed to assess whether three glycemic profiles [fasting glucose, fasting insulin, and glycated hemoglobin (HbA1c)] and five lipid profiles (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, non-HDL cholesterol, total cholesterol, and triglycerides) mediated the causal effect. Furthermore, Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were performed for sensitivity analyses.ResultsThe IVW results showed that SHBG significantly reduced SVS risk (odds ratio= 0.60, 95% confidence interval: 0.47-0.77, P = 4.60E-05). The weighted median and MR-Egger results were parallel to IVW. However, no significant associations were found between SHBG and AIS, CES, and LAS. Mediation analysis indicated that HbA1c may be involved in SHBG reducing SVS risk. Sensitivity tests demonstrated the reliability of causal estimates.ConclusionsCirculating SHBG levels may decrease SVS risk by lowering HbA1c levels. Therefore, individuals with low circulating SHBG levels should focus on glycemic control to reduce future SVS risk.© The Author(s) 2023. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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