Platform Science in Depth

Serum angiotensin-converting enzyme (ACE) is the universally adopted monitoring biomarker for sarcoidosis disease activity. Physicians use it to initiate therapy, track treatment response, and guide steroid tapering. But ACE monitoring fails in African American patients through three independent mechanisms identified by McGenome's founder:

Mechanism 1 - rs1799752 Polymorphism: The ACE gene I/D polymorphism at rs1799752 produces genotype-dependent baseline ACE differences of up to 30 U/L. The II genotype (homozygous insertion) is more prevalent in African ancestry populations, producing systematically lower ACE independent of disease activity.

Mechanism 2 - ACE Inhibitor Suppression: Approximately 50% of Black sarcoidosis patients take ACE inhibitors for comorbid hypertension - reducing serum ACE by 50-80% regardless of granuloma burden.

Mechanism 3 - Fibrotic Paradox: In progressive fibrosing sarcoidosis (Stage III-IV), ACE paradoxically falls as epithelioid macrophages are replaced by fibroblast-derived collagen, even as organ destruction accelerates.