Hu Jingqin, Mi Yuqiang, Wang Li, Jiang Feng, Li Ping
Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China; Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China.
Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300192, China.
Clin Res Hepatol Gastroenterol. 2024 Aug;48(7):102394. doi: 10.1016/j.clinre.2024.102394. Epub 2024 Jun 8.
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by elevated serum antimitochondrial antibody levels in 90-95 % of cases. However, the exact causal relationship between mitochondrial proteins and PBC remains unclear. This study aims to investigate and clarify this relationship.
Genome-wide association data for mitochondrial proteins and PBC were obtained from public databases. The assessment of causal relationships between exposures and outcomes employed the Inverse Variance Weighted (IVW) method, MR Egger regression, and Weighted Median. Sensitivity analyses were systematically carried out to appraise the robustness of the Mendelian Randomization (MR) findings.
The analysis revealed two mitochondrial proteins exhibiting a causal relationship with PBC. Elevated SIRT5 levels demonstrated a positive correlation with an augmented susceptibility to PBC in the IVW approach (odds ratio, OR: 1.2907, 95 % CI: 1.062-1.568, p = 0.0102). Conversely, increased MRPL33 levels were associated with a decreased risk of PBC (OR: 0.8957, 95 % CI: 0.807-0.993, p = 0.0376). Sensitivity analysis corroborated these findings consistently.
This investigation advances the notion of a potential causal association between elevated SIRT5 levels and an increased risk of PBC, alongside a decreased risk of PBC linked to elevated MRPL33 levels. The identified mitochondrial proteins may serve as viable biomarkers, offering pertinent insights for the understanding and addressing of PBC.
原发性胆汁性胆管炎（PBC）是一种自身免疫性肝病，90%-95%的病例血清抗线粒体抗体水平升高。然而，线粒体蛋白与PBC的确切因果关系仍不清楚。本研究旨在调查并阐明这种关系。
从公共数据库中获取线粒体蛋白和PBC的全基因组关联数据。采用逆方差加权（IVW）法、MR Egger回归和加权中位数评估暴露与结局之间的因果关系。系统地进行敏感性分析以评估孟德尔随机化（MR）结果的稳健性。
分析发现两种线粒体蛋白与PBC存在因果关系。在IVW方法中，SIRT5水平升高与PBC易感性增加呈正相关（优势比，OR：1.2907，95%可信区间：1.062-1.568，p = 0.0102）。相反，MRPL33水平升高与PBC风险降低相关（OR：0.8957，95%可信区间：0.807-0.993，p = 0.0376）。敏感性分析一致证实了这些发现。
本研究提出了SIRT5水平升高与PBC风险增加之间潜在因果关联的观点，以及MRPL33水平升高与PBC风险降低相关的观点。所确定的线粒体蛋白可能作为可行的生物标志物，为理解和应对PBC提供相关见解。
