• ACE I/D genotype shapes longitudinal serum ACE dynamics in sarcoidosis. • Baseline serum ACE levels did not differ significantly between genotypes. • The DD genotype shows the steepest decline in serum ACE over time. • Genotype effects emerge during longitudinal follow-up. • ACE genotyping may improve interpretation of serial ACE measurements. Serum angiotensin-converting enzyme (sACE) is widely used as a biomarker in sarcoidosis, yet interpretation is complicated by genetic variability. We investigated whether ACE insertion/deletion (I/D) genotype influences longitudinal sACE activity and its relationship to clinical manifestations and treatment response. Forty-six patients with confirmed sarcoidosis and available ACE genotype data were included. sACE activity was measured longitudinally and normalized to the assay-specific upper limit of normal (sACE index). Linear mixed modeling assessed genotype-specific trajectories over time. Organ involvement and treatment response were compared across genotypes. Genotype distribution was DD (35%), ID (41%), and II (24%). Baseline sACE index showed a descending numerical trend across genotypes but did not differ significantly. Longitudinal modeling demonstrated a significantly steeper decline in sACE index in DD compared with ID and II genotypes (p < 0.001 for interaction). Organ involvement and treatment response did not differ across genotypes. ACE I/D genotype influences longitudinal serum ACE activity in sarcoidosis. Genotype-informed interpretation may improve biomarker-based monitoring.
Leffers et al. (Sat,) studied this question.