The causal relationship between aspartate aminotransferase and hypertension: A bidirectional Mendelian randomization study

Hypertension is a major contributor to the global burden of disease and increased mortality in the general population. Currently, the etiology and pathogenesis of hypertension are not fully understood. Emerging evidence suggests an association between aspartate aminotransferase (AST) and hypertension, but whether this relationship is causal remains unclear. A two-sample MR analysis was conducted using GWAS summary data. Five MR methods – MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode – were applied, with IVW as the primary approach. Sensitivity analyses, including heterogeneity and pleiotropy assessments, as well as leave-one-out (LOO) analysis, were performed. Functional annotation of non-coding SNPs was conducted using the 3DSNP database, while GeneMania and enrichment analysis explored gene interactions and biological pathways. Forward MR analysis using the IVW method indicated a significant causal effect of AST on hypertension (<i>β</i> = 0.0003, Standard Error (SE) = 6.93E−05, <i>P</i> = 0.0002). However, reverse MR analysis found no significant causal relationship between hypertension and AST (<i>β</i> = 15.7148, SE = 12.7551 <i>P</i> = 0.2179). The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. These findings were robust across several reliability analyses. Finally, network and functional enrichment analyses showed that, under the influence of IVs, the SNP-hosted genes and AST promote disease progression through involvement in aspartic acid family metabolism and hexose biosynthesis. The present study reports the potential role of AST in the development of hypertension. The link between AST and hypertension may be due to regulation of substance and energy metabolism. These findings offer new insights into the pathophysiology of hypertension and suggest that AST could serve as a potential biomarker or therapeutic target for hypertension management.