Zhu Yingping, Li Zhenghong, Liu Xingfang, Wen Chengping
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
Research Department, Swiss University of Traditional Chinese Medicine, Bad Zurzach, Switzerland.
Front Genet. 2024 Sep 2;15:1336728. doi: 10.3389/fgene.2024.1336728. eCollection 2024.
While the hepatic enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) are crucial for liver function, their role in Spontaneous Abortion (SA) has not been thoroughly explored. Utilizing Mendelian Randomization (MR), this study aims to clarify the putative causal relationship between AST/ALT levels and SA.
Genome-wide association study (GWAS) summary data for SA (finn-b-O15_ABORT_SPONTAN), AST (ukb-d-30650_raw), and ALT (ukb-d-30620_raw) were acquired from the Integrative Epidemiology Unit OpenGWAS database. Bidirectional MR analysis was conducted using MR-Egger, Weighted Median, Simple Mode, Weighted Mode, and Inverse Variance Weighted (IVW) algorithms, and the robustness of MR results was assessed through sensitivity analyses including Heterogeneity, Horizontal Pleiotropy, and Leave-One-Out (LOO) tests. The causal role of AST and ALT's coaction in SA was explored via multivariable MR (MVMR) analysis.
The MR results via the IVW algorithm revealed a causal relation between both AST and ALT and SA (AST: = 0.013; ALT: = 0.017), identifying them as risk factors for SA (AST: odd ratio (OR) = 1.019; ALT: OR = 1.012). Sensitivity analysis substantiated the reliability of these results. Moreover, not notably causality was found between SA and AST/ALT ( > 0.05). Through MVMR analysis, AST and ALT demonstrated functional complementarity in the occurrence of SA, attributable to counterbalanced causalities (AST: = 0.128; ALT: = 0.899).
The study substantiates a causal linkage between transaminase levels and SA, enhancing our understanding of their biological interaction and the regulatory mechanisms at play. These insights could have implications for identifying novel biomarkers and therapeutic targets for SA.
虽然肝脏酶天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）对肝功能至关重要，但其在自然流产（SA）中的作用尚未得到充分研究。本研究利用孟德尔随机化（MR）来阐明AST/ALT水平与SA之间的假定因果关系。
从综合流行病学单位开放GWAS数据库中获取SA（finn-b-O15_ABORT_SPONTAN）、AST（ukb-d-30650_raw）和ALT（ukb-d-30620_raw）的全基因组关联研究（GWAS）汇总数据。使用MR-Egger、加权中位数、简单模式、加权模式和逆方差加权（IVW）算法进行双向MR分析，并通过包括异质性、水平多效性和留一法（LOO）检验在内的敏感性分析评估MR结果的稳健性。通过多变量MR（MVMR）分析探讨AST和ALT共同作用在SA中的因果作用。
通过IVW算法的MR结果显示AST和ALT与SA之间均存在因果关系（AST： = 0.013；ALT： = 0.017），将它们确定为SA的危险因素（AST：比值比（OR） = 1.019；ALT：OR = 1.012）。敏感性分析证实了这些结果的可靠性。此外，未发现SA与AST/ALT之间存在显著因果关系（ > 0.05）。通过MVMR分析，AST和ALT在SA的发生中表现出功能互补性，这归因于相互抵消的因果关系（AST： = 0.128；ALT： = 0.899）。
该研究证实了转氨酶水平与SA之间的因果联系，增进了我们对它们的生物学相互作用和所起调节机制的理解。这些见解可能对识别SA的新型生物标志物和治疗靶点具有启示意义。
