ACE I/D polymorphism

The ACE insertion/deletion (I/D) polymorphism (rs4646994) involves a 287-bp Alu repeat in intron 16 of the angiotensin-converting enzyme gene; the D allele is associated with approximately 1.5–2 times the serum ACE activity of the II genotype, influencing the renin-angiotensin-aldosterone system and thereby blood pressure regulation and cardiovascular tone. Early studies reported associations between the D allele and myocardial infarction risk, and between the I allele and elite endurance performance, though many of these findings have not replicated consistently in larger studies or meta-analyses. In the context of longevity, associations have been reported in several centenarian cohorts but the direction and magnitude are inconsistent across populations. The ACE I/D locus is best understood as a modest modulator of ACE enzyme levels with population-specific effects, rather than a robust longevity locus.