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<p>The pathogenesis of primary aldosteronism (PA) remains incompletely understood. Current pharmacological therapies have significant limitations, thus highlighting the importance of recognizing new therapeutic targets for the diagnosis and treatment of PA.&#xa0;This study employed two-sample Mendelian randomization (MR) analysis, colocalization, summary data-based Mendelian randomization (SMR) analysis, and mediation analysis to recognize new therapeutic targets for the diagnosis and treatment of PA.&#xa0;Our analysis revealed a significant positive connection between increased FES eQTL expression and reduced PA risk. Concurrently, to elucidate the underlying metabolic mechanisms through which the FES eQTL influences PA, we identified immune cells as significant mediators of this pathway. Specifically,&#xa0;The FES eQTL was found to elevate the risk level of CD3 expression on TD CD8br immune cells (OR = 1.116885, 95% CI = 1.037747–1.202059, <i>p</i> = 3.20E-03), whereas elevated CD3 expression on TD CD8br immune cells reduced the risk of PA (OR = 0.6382, 95% CI = 0.428972–0.949479, <i>p</i> = 2.67E-02). On the basis of the aforementioned relationships, we ultimately determined that FES suppresses PA through a potential metabolic mechanism that involves immune cell modulation.&#xa0;We identified and verified the FES eQTL as a new cis-eQTL-mediated susceptibility gene that can reduce the risk of PA among druggable genes. Concurrently, we observed that the FES eQTL suppresses PA through a potential metabolic mechanism that involves the regulation of CD3 on TD CD8br immune cells, thereby providing a new therapeutic target for PA diagnosis and treatment.</p>

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FES eQTL suppresses the progression of primary aldosteronism by regulating CD3 on TD CD8br immune cells: Mendelian randomization and mediation analysis

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Cai Deng,
  • Huasheng Liao,
  • Yizhao Wu,
  • Zijian Ao,
  • Lichao Zhang

摘要

The pathogenesis of primary aldosteronism (PA) remains incompletely understood. Current pharmacological therapies have significant limitations, thus highlighting the importance of recognizing new therapeutic targets for the diagnosis and treatment of PA. This study employed two-sample Mendelian randomization (MR) analysis, colocalization, summary data-based Mendelian randomization (SMR) analysis, and mediation analysis to recognize new therapeutic targets for the diagnosis and treatment of PA. Our analysis revealed a significant positive connection between increased FES eQTL expression and reduced PA risk. Concurrently, to elucidate the underlying metabolic mechanisms through which the FES eQTL influences PA, we identified immune cells as significant mediators of this pathway. Specifically, The FES eQTL was found to elevate the risk level of CD3 expression on TD CD8br immune cells (OR = 1.116885, 95% CI = 1.037747–1.202059, p = 3.20E-03), whereas elevated CD3 expression on TD CD8br immune cells reduced the risk of PA (OR = 0.6382, 95% CI = 0.428972–0.949479, p = 2.67E-02). On the basis of the aforementioned relationships, we ultimately determined that FES suppresses PA through a potential metabolic mechanism that involves immune cell modulation. We identified and verified the FES eQTL as a new cis-eQTL-mediated susceptibility gene that can reduce the risk of PA among druggable genes. Concurrently, we observed that the FES eQTL suppresses PA through a potential metabolic mechanism that involves the regulation of CD3 on TD CD8br immune cells, thereby providing a new therapeutic target for PA diagnosis and treatment.