Liu Yi-Ying, Zhang Yue-Yang, Wan Qin
Centre for Endocrine and Thyroid Diseases, Deyang People's Hospital, Deyang, 618000, China.
Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Sci Rep. 2025 Jan 27;15(1):3342. doi: 10.1038/s41598-025-88196-w.
With the rapid advancement of proteomics, numerous scholars have investigated the intricate relationships between plasma proteins and various diseases. Therefore, this study aims to elucidate the relationship between BDH1 and type 2 diabetes using Mendelian randomization (MR) and to identify novel targets for the prevention and treatment of type 2 diabetes through proteomics. This study primarily employed the Mendelian Randomization (MR) method, leveraging genetic data from numerous large-scale, publicly accessible genome-wide association studies (GWAS). Within this framework, we adopted a two-step, two-sample MR approach to evaluate the relationships between BDH1, plasma proteins, and type 2 diabetes. Finally, we conducted bidirectional MR analyses along with various sensitivity analyses to ensure the robustness and reliability of the study findings. The inverse variance weighted (IVW) analysis demonstrated that for each 1 standard deviation (SD) increase in BDH1, the risk of type 2 diabetes decreased by 3% (OR: 0.97; 95% CI: 0.95, 0.99). Concurrently, the proteomics-based MR analysis identified 37 plasma proteins associated with type 2 diabetes and 27 plasma proteins associated with BDH1. Notably, NBN, ARG1, and CCL11 were found to mediate the protective effect of BDH1 on type 2 diabetes. Our research findings uncovered the potential protective effect of BDH1 on type 2 diabetes and identified several plasma proteins associated with the disease. These results open new avenues for enhanced exploration of the prevention and treatment of type 2 diabetes.
随着蛋白质组学的迅速发展，众多学者研究了血浆蛋白与各种疾病之间的复杂关系。因此，本研究旨在利用孟德尔随机化（MR）阐明BDH1与2型糖尿病之间的关系，并通过蛋白质组学确定2型糖尿病预防和治疗的新靶点。本研究主要采用孟德尔随机化（MR）方法，利用来自众多大规模、可公开获取的全基因组关联研究（GWAS）的遗传数据。在此框架内，我们采用两步两样本MR方法来评估BDH1、血浆蛋白与2型糖尿病之间的关系。最后，我们进行了双向MR分析以及各种敏感性分析，以确保研究结果的稳健性和可靠性。逆方差加权（IVW）分析表明，BDH1每增加1个标准差（SD），2型糖尿病风险降低3%（OR：0.97；95%CI：0.95，0.99）。同时，基于蛋白质组学的MR分析确定了37种与2型糖尿病相关的血浆蛋白和27种与BDH1相关的血浆蛋白。值得注意的是，发现NBN、ARG1和CCL11介导BDH1对2型糖尿病的保护作用。我们的研究结果揭示了BDH1对2型糖尿病的潜在保护作用，并确定了几种与该疾病相关的血浆蛋白。这些结果为加强2型糖尿病预防和治疗的探索开辟了新途径。
