Apoe4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical amerindian subsistence population

Angela R. Garcia, Caleb Finch, Margaret Gatz, Thomas Kraft, Daniel Eid Rodriguez, Daniel Cummings, Mia Charifson, Kenneth Buetow, Bret A. Beheim, Hooman Allayee, Gregory S. Thomas, Jonathan Stieglitz, Michael D. Gurven, Hillard Kaplan, Benjamin C. Trumble

Research output: Contribution to journalArticlepeer-review

Abstract

In post-industrial settings, apolipoprotein E4 (APOE4) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypoth-esize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N = 1266, 50 % female), APOE4 is associated with 30 % lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between APOE4 and lipids may be bene-ficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.

Original languageEnglish (US)
Article numbere68231
JournaleLife
Volume10
DOIs
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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