ANGIOTENSIN-1-CONVERTING ENZYME (ACE) GENE POLYMORPHISM, PLASMA ACE LEVELS, AND THEIR ASSOCIATION WITH THE METABOLIC SYNDROME AND ELECTROCARDIOGRAPHIC CORONARY-ARTERY DISEASE IN PIMA-INDIANS

In Caucasian subjects, an insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with coronary artery disease (CAD) and fatal myocardial infarction. The underlying m echanism(s) of this association is not fully understood. Pima Indians have a low incidence of nonfatal and fatal CAD despite a high prevalen ce of diabetes. In Pima Indians, circulating ACE levels are related to ACE genotype, but the frequency of the D allele is significantly lowe r than in Caucasians. A lower frequency of the D allele may underlie a low risk of CAD in this population. We examined the relationship of t he ACE genotype and plasma ACE level with electrocardiographic evidenc e of CAD (Tecumseh criteria), hypertension, and metabolic variables as sociated with insulin resistance in 305 (146 men and 159 women aged 47 +/- 9.0 years) Pima Indians characterized for the ACE I/D genotype. T he distribution of ACE genotypes was unrelated to diabetes and obesity . Easting plasma insulin, plasminogen activator inhibitor-1 (PAI-1) ac tivity, plasma triglyceride concentrations, and systolic (SBP) and dia stolic (DBP) blood pressure were not significantly different between t he three ACE genotypes among nondiabetic and diabetic subjects. There was no significant association of ACE genotype with electrocardiograph ic evidence of CAD or with hypertension. Plasma ACE concentrations wer e not significantly different between nondiabetic and diabetic subject s (median, 77 [range, 21 to 169] v 83 [7 to 238] IU/mL, P = NS). In al l subjects, plasma ACE levels were associated weakly with plasma trigl yceride (partial r =.20, P <.01) and total cholesterol (partial r =.13 , P <.03) concentrations, but not with fasting plasma insulin or PAI-1 activity. In diabetic subjects, ACE levels were related to fasting pl asma glucose concentrations (partial r =.15, P =.07). These findings w ould suggest that ACE gene I/D polymorphism is unlikely to be a major determinant of susceptibility to CAD in Pima Indians. Plasma ACE level s, but not ACE genotype, correlated with lipids, plasma glucose, and b lood pressure, suggesting that elevated plasma ACE levels may contribu te to the link between insulin resistance and CAD disease or may be a consequence of it. Copyright (C) 1998 by W.B. Saunders Company.