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.