# ACE I/D polymorphism

The ACE insertion/deletion (I/D) polymorphism (rs4646994) is a 287-base-pair stretch of DNA (an Alu repeat). It is either present or absent in intron 16 of the ACE gene. The D ('deletion') allele goes with roughly 1.5 to 2 times the serum ACE activity of the II genotype. That influences the renin-angiotensin-aldosterone system. And so it shapes your blood-pressure control and cardiovascular tone. Early studies linked the D allele to heart-attack risk, and the I allele to elite endurance performance. But many of those findings have not replicated cleanly in larger studies. For longevity, associations have shown up in several centenarian groups. But the direction and size are inconsistent across populations. So the ACE I/D site is best understood as a modest dial on ACE enzyme levels, with population-specific effects, not a strong longevity locus.

## Sources

- Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. (1990). An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. Journal of Clinical Investigation. https://doi.org/10.1172/JCI114844
- Li Y, Murakami S. (2023). Artificial Intelligence-Assisted Meta-Analysis of the Frequency of ACE I/D Polymorphisms in Centenarians and Other Long-Lived Individuals. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms24043411

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_Canonical: https://longevity-switzerland.com/en/glossary/ace-i-d-polymorphism · Part of Longevity Cities · Updated 2026-06-22_