Genetics of angiotensin I-converting enzyme

The ACE gene is constitutively expressed in several types of somatic cells, including vascular cells. A soluble form of the enzyme is secreted in plasma by proteolytic cleavage of the membrane anchor. The interindividual variability in plasma ACE levels is very large, and a family study has indicated that it was under the influence of a major gene polymorphism. An insertion (I) deletion (D) polymorphism in intron 16 of the ACE gene was then found to be associated with plasma and cellular ACE levels. The D allele, which is associated with higher plasma ACE levels, and the level of ACE in plasma, were found in case control studies to be associated with an increased risk of myocardial infarction, an increased risk of diabetic nephropathy in type I diabetic patients, and a faster rate of renal function degradation in glomerular diseases. Although these findings should be confirmed in prospective studies, they can support the concept that ACE level is a critical factor in the determinism of angiotensins and kinins (and perhaps also other peptide substrates) levels in peripheral circulations and in tissue interstitium, especially in the heart and kidney.