Exploring the link between antihypertensive drugs targets and pancreatitis risk through Mendelian randomization

Observational studies indicate an association between antihypertensive drugs and the risk of acute pancreatitis (AP) and chronic pancreatitis (CP). This study aims to utilize Mendelian randomization (MR) analysis to assess the causal impact of antihypertensive drugs on the risk of AP and CP.

Protein target information for eight commonly used antihypertensive drugs was collected from the DrugBank database. The inverse variance-weighted (IVW) method was the primary approach used to investigate the association between genetic instruments from the discovery cohorts and the risk of AP and CP. The presence of heterogeneity was determined using Cochran's Q test.

The genetic proxies of angiotensin-converting enzyme inhibitors (ACEIs) were identified as risk factors for AP. Genetic proxies for potassium-sparing diuretics (PSDs) were found to have a positive causal relationship with the occurrence of AP. In contrast, β-blockers (BBs) and loop diuretics were identified as protective factors against AP. Genetic proxies of ACEIs were identified as risk factors for CP, whereas BBs were found to be protective factors for CP. Additionally, genetic proxies for PSDs showed a protective effect on CP, while loop diuretics were identified as risk factors for CP.

BBs may have a protective effect on AP, whereas ACEIs and PSDs may have negative effects. The genetic proxies of PSDs and BBs are protective factors for CP, while the genetic proxies of ACEIs and loop diuretics are risk factors for CP.