GENETICS OF ANGIOTENSIN I-CONVERTING ENZYME

The ACE gene is constitutively expressed in several types of somatic c ells, including vascular cells. A soluble form of the enzyme is secret ed in plasma by proteolytic cleavage of the membrane anchor. The inter individual variability in plasma ACE levels is very large, and a famil y 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 cellul ar ACE levels. The D allele, wich is associated with higher plasma ACE levels, and the level of ACE in plasma, were found in case control st udies to be associated with an increased risk of myocardial infarction , an increased risk of diabetic nephropathy in type I diabetic patient s, and a faster rate of renal function degradation in glomerular disea ses. Although these findings should be confirmed in prospective studie s, they can support the concept that ACE level isa critical factor in the determinism of angiotensins and kinins (and perhaps also other pep tide substrates) levels in peripheral circulations and in tissue inter stitium, especially in the heart and kidney.