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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Nutritional Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1408347

Genetically Predicted HLA-DR+ Natural Killer Cells as Potential Mediators in the Lipid-Coronary Artery Disease Causal Pathway

Provisionally accepted
Dingding Qian Dingding Qian *Haoyue Zhang Haoyue Zhang Rong Liu Rong Liu Honghua Ye Honghua Ye
  • Ningbo University, Ningbo, China

The final, formatted version of the article will be published soon.

    Background: Coronary artery disease (CAD) imposes a significant global health burden, necessitating a deeper comprehension of its genetic foundations to uncover innovative therapeutic targets. Employing a comprehensive Mendelian randomization (MR) approach, we aimed to explore the genetic associations between lipid profiles, immune cell phenotypes, and CAD risk.Methods: Utilizing data from recent large-scale genome-wide association studies (GWAS), we scrutinized 179 lipid and 731 immune cell phenotypes to delineate their genetic contributions to CAD pathogenesis, including coronary artery calcification (CAC). Moreover, specific immune cell phenotypes were examined as potential mediators of the lipid-CAD causal pathway.Results: Among the 162 lipid species with qualified instrumental variables (IVs) included in the analysis, we identified 36 lipids that exhibit a genetic causal relationship with CAD, with 29 being risk factors and 7 serving as protective factors.Phosphatidylethanolamine (18:0_20:4) with 8 IVs (OR, 95% CI, P-value: 1.04, 1.02-1.06, 1.50E-04) met the Bonferroni-corrected significance threshold (0.05/162 = 3.09E-04). Notably, all 18 shared lipids were determined to be risk factors for both CAD and CAC, including 16 triacylglycerol traits (15 of which had ≥ 3 IVs), with (50:1) exhibiting the highest risk [OR (95% CI) in CAC: 1.428 (1.129-1.807); OR (95% CI) in CAD: 1.119 (1.046-1.198)], and 2 diacylglycerol traits. Furthermore, we identified HLA DR+ natural killer cells (IVs = 3) as nominally significant with lipids and as potential mediators in the causal pathway between diacylglycerol (16:1_18:1) or various triacylglycerols and CAD (mediated effect: 0.007 to 0.013).This study provides preliminary insights into the genetic correlations between lipid metabolism, immune cell dynamics, and CAD susceptibility, highlighting the potential involvement of natural killer cells in the lipid-CAD causal pathway and suggesting new targets for therapy. Further evidence is necessary to substantiate our findings.

    Keywords: Coronary Artery Disease, Mendelian randomization, Lipidome, immune cell, Natural Killer cell

    Received: 28 Mar 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Qian, Zhang, Liu and Ye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Dingding Qian, Ningbo University, Ningbo, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.