Parallel effects of genetic variation in ACE activity in baboons and humans.

Published

Journal Article

Like humans, savannah baboons (Papio sp.) show heritable interindividual variation in complex physiological phenotypes. One prominent example of such variation involves production of the homeostatic regulator protein angiotensin converting enzyme (ACE), which shows heritable variation in both baboons and humans. In humans, this phenotypic variation is associated with an Alu insertion-deletion polymorphism in the ACE gene, which explains approximately half of the variation in serum ACE activity. We identified a similar Alu insertion-deletion polymorphism in the baboon ACE homologue and measured its frequency in a wild population and a captive population of baboons. We also analyzed the contribution of ACE genotype at this indel to variation in serum ACE activity in the captive population. When conditioned on weight, a known factor affecting ACE activity in humans, age and ACE genotype both accounted for variance in ACE activity; in particular, we identified a significant nonadditive interaction between age and genotype. A model incorporating this interaction effect explained 21.6% of the variation in residual serum ACE activity. Individuals homozygous for the deletion mutation exhibited significantly higher levels of ACE activity than insertion-deletion heterozygotes at younger ages (10-14 years), but showed a trend towards lower levels of ACE activity compared with heterozygotes at older ages (> or =15 years). These results demonstrate an interesting parallel between the genetic architecture underlying ACE variation in humans and baboons, suggesting that further attention should be paid in humans to the relationship between ACE genetic variation and aging.

Full Text

Duke Authors

Cited Authors

  • Tung, J; Rudolph, J; Altmann, J; Alberts, SC

Published Date

  • September 2007

Published In

Volume / Issue

  • 134 / 1

Start / End Page

  • 1 - 8

PubMed ID

  • 17503445

Pubmed Central ID

  • 17503445

Electronic International Standard Serial Number (EISSN)

  • 1096-8644

International Standard Serial Number (ISSN)

  • 0002-9483

Digital Object Identifier (DOI)

  • 10.1002/ajpa.20614

Language

  • eng