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免疫细胞与痛风之间的因果关系:一项双向两样本孟德尔随机化研究。

The causal association between immune cells and gout: A bidirectional two-sample Mendelian randomization study.

机构信息

Department of Rheumatology and Immunology, Yulin First People's Hospital, Yulin, Guangxi Zhuang Autonomous Region, China.

Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

出版信息

Medicine (Baltimore). 2024 Oct 18;103(42):e40064. doi: 10.1097/MD.0000000000040064.

Abstract

Gout, a metabolic disorder, is increasingly being linked to immune cells. However, the causal relationships between these factors remain unclear. Our study aimed to elucidate the causal relationship between immune cells and gout. Our study used 2-sample Mendelian randomization (MR) to explore the causal relationship between immune cells and gout. It is noteworthy that we utilized 5 methods MR-Egger, weighted median, inverse variance weighted, weighted mode, and simple mode to ensure the reliability of the results. Comprehensive sensitivity analyses were performed to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. After false discovery rate correction (PFDR <0.20), 3 immunophenotypes were identified: one in the B cell panel, one in the regulatory T cells panel, and another in the T lymphocytes, B lymphocytes, Natural Killer cells panel. Among them, 2 immunophenotypes (CD4-CD8-T cell absolute count and CD25 on IgD + CD24 + B cell) increased the risk of developing gout, whereas the other one immunophenotype (CD45RA + CD28- CD8 + T cell %T cell) decreased the risk of gout. Subsequently, we did not observe heterogeneity and horizontal pleiotropy stable in these data through comprehensive sensitivity analyses. Furthermore, we identified some positive results in reverse MR analysis, but after false discovery rate correction (PFDR <0.20), no significant results were detected. Our study revealed causal relationships between immune cells and gout, providing novel insights into the prevention and treatment of gout.

摘要

痛风是一种代谢紊乱性疾病,越来越多的证据表明其与免疫细胞有关。然而,这些因素之间的因果关系仍不清楚。本研究旨在阐明免疫细胞与痛风之间的因果关系。本研究使用两样本 Mendelian 随机化(MR)来探索免疫细胞与痛风之间的因果关系。值得注意的是,我们使用了 5 种 MR-Egger、加权中位数、逆方差加权、加权模式和简单模式来确保结果的可靠性。综合敏感性分析用于验证结果的稳健性、异质性和水平多效性。经过错误发现率校正(PFDR <0.20),鉴定出 3 种免疫表型:B 细胞组中的 1 种、调节性 T 细胞组中的 1 种和 T 淋巴细胞、B 淋巴细胞、自然杀伤细胞组中的 1 种。其中,2 种免疫表型(CD4-CD8-T 细胞绝对计数和 IgD+CD24+CD25+B 细胞)增加了痛风的发病风险,而另一种免疫表型(CD45RA+CD28-CD8+T 细胞%T 细胞)降低了痛风的发病风险。随后,我们通过综合敏感性分析发现这些数据中不存在异质性和水平多效性。此外,我们在反向 MR 分析中发现了一些阳性结果,但经过错误发现率校正(PFDR <0.20)后,未检测到显著结果。本研究揭示了免疫细胞与痛风之间的因果关系,为痛风的预防和治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2506/11495775/e2ad8befc427/medi-103-e40064-g001.jpg

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