Comparative analysis of genes regulating HDL function and metabolism in macaques and humans

The role of the high density lipoprotein (HDL) molecule is currently an area of great interest within the scientific community. Previously, mouse and human studies have demonstrated an inverse association between HDL cholesterol (HDL-C) levels and cardiovascular disease. Recent clinical trials, which increased HDL-C, have failed to reduce the number of cardiovascular disease events. This suggests a need for a new model of HDL biology in order to better understand the relationship between cardiovascular risk and HDL function. Rhesus macaques are a potentially valuable animal model for analysis of HDL because many animals present with clinically relevant levels of HDL-C while maintaining normal levels of other related lipids, removing common confounding factors. Our findings show that genetic variation in selected genes related to disorders of HDL metabolism and function is highly conserved between rhesus macaques and humans. We also find suggestive evidence that genetic variation associated with human HDL disorders is also associated with HDL phenotypes in macaques. We conclude that the rhesus macaque is a valuable model for human HDL biology