Chen Jie, Ruan Xixian, Sun Yuhao, Li Xue, Yuan Shuai, Larsson Susanna C
Center for Global Health, Zhejiang University School of Medicine, Hangzhou, China; Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.
Nutrition. 2023 Feb;106:111910. doi: 10.1016/j.nut.2022.111910. Epub 2022 Nov 6.
The role of plasma phospholipid arachidonic acid (AA) in the development of non-alcoholic fatty liver disease (NALFD), cirrhosis, and liver cancer remains unclear. This study aimed to determine the causality of the associations of plasma phospholipid AA with NALFD, cirrhosis, and liver cancer using Mendelian randomization analysis.
Nine independent single-nucleotide polymorphisms associated with plasma phospholipid AA at the genome-wide significance were used as instrumental variables. Summary-level data for three outcomes were obtained from 1) a genome-wide association study for NAFLD, 2) the UK Biobank study, and 3) the FinnGen study. The sensitivity analysis excluding the pleiotropic variant rs174547 in the FADS1 gene was performed. Estimates from different sources were combined using the fixed-effects meta-analysis method.
Per standard deviation increase in AA levels, the combined odds ratio was 1.06 (95% confidence interval, 1.02-1.11; P = 0.008) for NAFLD, 1.05 (95% confidence interval, 1.01-1.09; P = 0.009) for cirrhosis, and 0.99 (95% confidence interval, 0.94-1.05; P = 0.765) for liver cancer. The associations remained stable in the sensitivity analysis excluding rs174547.
This study suggests potential causal associations of high levels of plasma phospholipid AA with the risk of NAFLD and cirrhosis.
血浆磷脂花生四烯酸（AA）在非酒精性脂肪性肝病（NALFD）、肝硬化和肝癌发生发展中的作用尚不清楚。本研究旨在利用孟德尔随机化分析确定血浆磷脂AA与NALFD、肝硬化和肝癌之间关联的因果关系。
将9个在全基因组水平上与血浆磷脂AA相关的独立单核苷酸多态性用作工具变量。三个结局的汇总数据分别来自：1）一项关于非酒精性脂肪性肝病的全基因组关联研究；2）英国生物银行研究；3）芬兰基因研究。进行了排除FADS1基因中多效性变异rs174547的敏感性分析。采用固定效应荟萃分析方法合并来自不同来源的估计值。
AA水平每增加一个标准差，非酒精性脂肪性肝病的合并比值比为1.06（95%置信区间为1.02 - 1.11；P = 0.008），肝硬化为1.05（95%置信区间为1.01 - 1.09；P = 0.009），肝癌为0.99（95%置信区间为0.94 - 1.05；P = 0.765）。在排除rs174547的敏感性分析中，这些关联仍然稳定。
本研究提示血浆磷脂AA水平升高与非酒精性脂肪性肝病和肝硬化风险之间可能存在因果关联。
