Worldwide allele frequencies of the human apolipoprotein E gene: Climate, local adaptations, and evolutionary history

Abstract

The epsilon4 allele of the apolipoprotein E (APOE) gene is associated with increased cholesterol levels and heart disease. Population allele frequencies of APOE have previously been shown to vary, with epsilon4 frequencies generally increasing with latitude. We hypothesize that this trend resulted from natural selection protecting against low-cholesterol levels. In high-latitude cold environments and low-latitude hot environments, metabolic rate is elevated, which could require higher cholesterol levels. To explore this hypothesis, we compiled APOE allele frequencies, latitude, temperature, and elevation from populations around the world. epsilon4 allele frequencies show a curvilinear relationship with absolute latitude, with lowest frequencies found in the mid-latitudes where temperatures generally require less expenditure on cooling/thermogenesis. Controlling for population structure in a subset of populations did not appreciably change this pattern of association, consistent with selection pressures that vary by latitude shaping epsilon4 allele frequencies. Temperature records also predict APOE frequency in a curvilinear fashion, with lowest epsilon4 frequencies at moderate temperatures. The model fit between historical temperatures and epsilon4 is less than between latitude and epsilon4, but strengthened after correcting for estimated temperature differences during the Paleolithic. Contrary to our hypothesis, we find that elevation did not improve predictive power, and an integrated measure of the cholesterol effect of multiple APOE alleles was less related to latitude than was epsilon4 alone. Our results lend mixed support for a link between past temperature and human APOE allele distribution and point to the need to develop better models of past climate in future analyses.

Changing Trend of Overweight and Obesity and Their Associated Factors in an Urban Population of Bangladesh

“…This rapid urbanization has been associated with reduced open spaces. Environmental pollution [27,28], climate change [29,30] and increasing access to day-to-day modern amenities may also contribute to promoting sedentary lifestyles. Additionally, changes in dietary habits especially of children and young adults towards non-traditional foods with higher amounts of fats [31,32] may also be contributing to the increase in overweight and obesity.…”

ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

“…selection and not due to underlying population structure (12) . Generally apoE e4 is more present in people either with dark skin pigmentation or living in regions with low insolation, while lower presence is found in people with moderate melanin pigmentation but exposed to relatively high solar irradiation.…”

Human Apolipoprotein E ε4 Expression Impairs Cerebral Vascularization and Blood—Brain Barrier Function in Mice

“…2 ApoE is a polymorphic protein, which exists in humans as three isoforms ε2, ε3, and ε4 with worldwide frequencies of 6.4 ± 5.1%, 78.3 ± 12.1%, and 14.5 ± 8.5%, respectively. 1,3 Prevalence of APOE4 allele is about 37% in AD patients, a proportion three times higher than in the general population. 4 The three isoforms differ from each other only by the amino acids located at positions 112 and 158, leading to alterations in apoE structure and in its affinity toward its ligands and receptors, and thus in its role in neuropathologic conditions.…”