Zou Juanjuan, Zhang Yijing, Sun Xiaojing, Wang Yan, Li Yanzhong, Zhao Ze-Hua
Department of Otorhinolaryngology, Qilu Hospital of Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, China.
Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
Virulence. 2025 Dec;16(1):2553786. doi: 10.1080/21505594.2025.2553786. Epub 2025 Sep 4.
The association between chronic hepatitis B virus (HBV) infection and metabolic syndrome (MetS) remains controversial. We aimed to analyze the causal effects of chronic HBV infection on MetS components and vice versa. Mendelian randomization (MR) was applied to explore the genetic association of chronic HBV infection with both metabolic risk factors and metabolic diseases using summary-level data from GWAS. Further colocalization and mediation analyses were performed for traits with significant causal relationships. The effect of HBV on lipid metabolism was validated by assays. In European populations, the MR analyses did not support causal relationships between chronic HBV infection and metabolic traits. In East Asian populations, chronic HBV infection was associated with decreased low-density lipoprotein (LDL) and reduced risk of coronary artery disease (CAD). Reversely, CAD showed negative causal effects on chronic HBV infection risk. Colocalization analysis revealed that the association between chronic HBV infection and CAD was most likely driven by distinct rather than shared causal variants. Mediation analysis identified LDL as a major mediator in the causal effect of chronic HBV infection on CAD and aspirin use as the primary mediator in the causal effect of CAD on chronic HBV infection. experiments suggested that HBV may inhibit glucose plus insulin-induced lipogenesis in hepatocytes. Our results provide genetic evidence of chronic HBV infection as a protective factor against dyslipidemia and CAD and reveal the potential causal effect of CAD on genetically proxied chronic HBV infection via aspirin treatment in East Asian populations.
慢性乙型肝炎病毒（HBV）感染与代谢综合征（MetS）之间的关联仍存在争议。我们旨在分析慢性HBV感染对代谢综合征各组分的因果效应，反之亦然。采用孟德尔随机化（MR）方法，利用全基因组关联研究（GWAS）的汇总水平数据，探讨慢性HBV感染与代谢危险因素及代谢性疾病的遗传关联。对具有显著因果关系的性状进行了进一步的共定位和中介分析。通过实验验证了HBV对脂质代谢的影响。在欧洲人群中，MR分析不支持慢性HBV感染与代谢性状之间的因果关系。在东亚人群中，慢性HBV感染与低密度脂蛋白（LDL）降低及冠状动脉疾病（CAD）风险降低相关。反之，CAD对慢性HBV感染风险显示出负向因果效应。共定位分析表明，慢性HBV感染与CAD之间的关联最有可能由不同而非共享的因果变异驱动。中介分析确定LDL是慢性HBV感染对CAD因果效应的主要中介因素，而阿司匹林的使用是CAD对慢性HBV感染因果效应的主要中介因素。实验表明，HBV可能抑制葡萄糖加胰岛素诱导的肝细胞脂肪生成。我们的研究结果提供了遗传证据，证明慢性HBV感染是预防血脂异常和CAD的保护因素，并揭示了在东亚人群中，CAD通过阿司匹林治疗对遗传代理的慢性HBV感染的潜在因果效应。
