The Complex Genetic Basis of Plasma Triglycerides

Demonstration of a direct relationship between plasma triglyceride (TG) concentration and atherosclerosis has proven difficult due to confounding variables that accompany elevated plasma TG, such as other dyslipidemias, obesity, and type 2 diabetes. However, human genetic studies have provided evidence suggesting a causal link between plasma TG and cardiovascular risk. Analyses in human patients with hypertriglyceridemia (HTG) also provides insight into the relationship between genetic variation, predisposition to elevated plasma TG, and risk of subsequent cardiovascular disease. Here, we review recent key studies that have contributed to our understanding of the genetic determinants of plasma TG concentration, including HTG susceptibility and phenotypic heterogeneity, and discuss our maturing model of the allelic and phenotypic spectrum of plasma TG.