Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism with Increased Susceptibility to Vasculitis: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aimed to evaluate the association between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and susceptibility to vasculitis, including Henoch- Schönlein purpura (HSP), Henoch-Schönlein purpura nephritis (HSPN), and Behçet's disease (BD). METHODS: Relevant studies were systematically retrieved from PubMed, Embase, and Google Scholar until November 2025. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using different genetic models. Heterogeneity was assessed using the Cochrane Q test and I2 statistics, and random-effects models were applied. Statistical analyses were performed using the Review Manager (version 5.4). RESULTS: Fifteen eligible studies, including five on HSP, four on HSPN, and six on BD, were included, with a total of 1,536 cases and 1,947 controls. Pooled analysis demonstrated a significant association between the ACE I/D polymorphism and an increased risk of vasculitis (D vs. I, OR = 1.42, 95% CI 1.15-1.76), with stronger associations observed in Caucasian populations. Subgroup analysis revealed that the D allele was significantly associated with higher susceptibility to HSP and BD, whereas a modest association was detected for HSPN in the allelic comparison model. CONCLUSION: The findings suggest that the ACE D allele may be a genetic risk factor for vasculitic disorders, especially HSP and BD, supporting the possible involvement of the renin-angiotensin system in the development of autoimmune vascular inflammation.