Center for Evolution and Medicine, Arizona State University, Tempe, United States; Department of Anthropology, Emory University, Atlanta, United States
Center for Economic and Social Research, University of Southern California, Los Angeles, Los Angeles, United States
Thomas Kraft
Department of Anthropology, University of California, Santa Barbara, Santa Barbara, United States
Daniel Eid Rodriguez
Department of Medicine, Universidad de San Simón, Cochabamba, Bolivia
Daniel Cummings
Institute for Economics and Society, Chapman University, Orange, United States
Mia Charifson
Vilcek Institute of Graduate Biomedical Sciences, New York University, New York, United States
Kenneth Buetow
Center for Evolution and Medicine, Arizona State University, Tempe, United States; School of Life Sciences, Arizona State University, Tempe, United States
Bret A Beheim
Department of Human Behavior, Ecology and Culture, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
Department of Preventive Medicine and Biochemistry & Molecular Medicine, Keck School of Medicine, University of Southern California, Irvine, Irvine, United States; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Irvine, Irvine, United States
Gregory S Thomas
Long Beach Memorial, Long Beach and University of California Irvine, Irvine, United States
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 hypothesize 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 beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.
