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Causal effect of interleukin (IL)-6 on blood pressure and hypertension: A mendelian randomization study

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Abstract

To examine whether circulating interleukin-6 (IL-6) levels (CirIL6) have a causal effect on blood pressure using Mendelian randomization (MR) methods. We used data from genome-wide association studies (GWAS) of European ancestry to obtain genetic instruments for circulating IL-6 levels and blood pressure measurements. We applied several robust MR methods to estimate the causal effects and to test for heterogeneity and pleiotropy. We found that circulating IL-6 had a significant positive causal effect on systolic blood pressure (SBP) and pulmonary arterial hypertension (PAH), but not on diastolic blood pressure (DBP) or hypertension. We found that as CirIL6 genetically increased, SBP increased using Inverse Variance Weighted (IVW) method (for ukb-b-20175, β = 0.082 with SE = 0.032, P = 0.011; for ukb-a-360, β = 0.075 with SE = 0.031, P = 0.014) and weighted median (WM) method (for ukb-b-20175, β = 0.061 with SE = 0.022, P = 0.006; for ukb-a-360, β = 0.065 with SE = 0.027, P = 0.014). Moreover, CirIL6 may be associated with an increased risk of PAH using WM method (odds ratio (OR) = 15.503, 95% CI, 1.025–234.525, P = 0.048), but not with IVW method. Our study provides novel evidence that circulating IL-6 has a causal role in the development of SBP and PAH, but not DBP or hypertension. These findings suggest that IL-6 may be a potential therapeutic target for preventing or treating cardiovascular diseases and metabolic disorders. However, more studies are needed to confirm the causal effects of IL-6 on blood pressure and to elucidate the underlying mechanisms and pathways.

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The original contributions presented in this study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

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Acknowledgements

We are immensely grateful to the study participants in the GWAS, the data of which we used.

Funding

This work was supported by Advanced Project of of Zhejiang Shuren University(2024XZ012), grants from the National Natural Science Foundation of China (81102200), and “Teacher professional development project” for domestic visiting scholars in colleges and universities of Zhejiang Province in 2020[2020043].

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  1. Ou Wu and Ya Wu are first co-authors.

Authors and Affiliations

  1. Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang, People’s Republic of China

    Ou Wu

  2. Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China

    Ou Wu

  3. Anhui Medical University, Hefei, Anhui, People’s Republic of China

    Ya Wu

  4. Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Xingyu Zhang

  5. JFIntelligent Healthcare Technology Co., Ltd Building No.5-7, No.699 Tianxiang Avenue, Hi-Tech Zone, Nanchang, Jiangxi Province, People’s Republic of China

    Wei Liu

  6. Department of Thoracic Surgery, Sir Run Run Shaw Hospital Affiliated with Medical College of Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China

    Hu Zhang

  7. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, People’s Republic of China

    Saber Khederzadeh

  8. Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, People’s Republic of China

    Saber Khederzadeh

  9. Hangzhou Vocational and Technical College, Hangzhou, Zhejiang, People’s Republic of China

    Xi Lu

  10. School of Medicine, Shaoxing University, Shaoxing, Zhejiang, People’s Republic of China

    Xiao-Wei Zhu

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  1. Ou Wu
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Contributions

Ou Wu: Conceptualization, Data curation, Writing – original draft, Methodology, Supervision, Validation, Funding acquisition, Project administration, Formal analysis. Ya Wu: Methodology, Software, Data curation, Formal analysis, Writing – original draft. Xingyu Zhang: Software. Hu Zhang: Data curation. Wei Liu: Software. Saber Khederzadeh: Software. Xi Lu: Conceptualization, Data curation, Formal analysis, Writing – original draft, Methodology, Supervision, Validation. Xiao-wei Zhu: Conceptualization, Data curation, revision. 

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Correspondence to Ou Wu, Xi Lu or Xiao-Wei Zhu.

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All data used in this study were obtained from GWAS, with prior ethical approval and patient consent. The study protocol complied with the guidelines of the Declaration of Helsinki and was approved by the ethics committees of all participating sites.

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All the authors declare that they have no competing interests.

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Wu, O., Wu, Y., Zhang, X. et al. Causal effect of interleukin (IL)-6 on blood pressure and hypertension: A mendelian randomization study. Immunogenetics 76, 123–135 (2024). https://doi.org/10.1007/s00251-024-01332-0

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