Lack of association between the angiotensin-converting enzyme insertion/deletion polymorphism and plasminogen activator inhibitor-1 antigen levels inthe National Heart, Lung, and Blood Institute Family Heart Study

Experimental and clinical research supports a direct link between activatio n of the renin-angiotensin system and production of plasminogen activator i nhibitor-1 (PAI-1), the primary physiologic inhibitor of tissue plasminogen activator. Several studies have reported higher PAI-1 levels in individual s carrying the deletion (D) allele of the angiotensin-converting enzyme (AC E) gene. We investigated the association between ACE genotypes and plasma P AI-1 levels in a family study of 577 women and 428 men from four US communi ties. Participants were between 25 and 84 years of age without evidence of coronary heart disease (CHD). Mean geometric plasma PAI-1 levels adjusted f or ethnicity were 17.4, 17.9, and 18.1 ng/ml in participants with the DD, i nsertion-deletion (ID), and II genotypes, respectively (P = 0.89 for differ ence). We found no associations between ACE I/D genotypes and plasma PAI-1 antigen concentrations in a subset of participants without major CHD risk f actors (hypertension, hypercholesterolemia, overweight, smoking, diabetes) or in a small sample of African-Americans. Our findings suggest that the AC E insertion/deletion polymorphism has relatively little, if any, influence on circulating PAI-1 levels in the population at large. Blood Coagul Fibrin olysis 11:551-558 (C) 2000 Lippincott Williams & Wilkins.