Genetic basis of hypertriglyceridemies

Abstract

Diagnosis and treatment of triglyceride metabolism disorders: from pathophysiology to clinical practice. Hypertriglyceridaemia (HTG) affects 15%-20% of the world's population, and is frequently discovered as an incidental finding in a laboratory test. Disorders of triglyceride (TG) metabolism have a complex genetic basis. New genetic tools that allow a more precise approach to the disorders have made it possible to redefine and classify HTG into two groups: monogenic HTG (TG>10 mmol/L) and polygenic HTG (2 mmol/L<TG<10 mmol/L) with a milder phenotype, but with a clear genetic influence. In approximately 50% of patients with severe HTG a genetic cause has not yet been found. In addition to the inclusion of ever more genes in studies, statistical models are now also being examined that consider complex gene-environment interactions that could explain why the presence of a set of apparently benign variants may cause HTG in the presence of a triggering factor such as adiposity. Knowledge of the genetic nature of HTG has also helped identify targets for pharmacological treatments, thus avoiding a strict diet with a fat content of less than 20%, which is difficult to maintain. Accurate diagnosis of these disorders is essential for correct treatment according to the inherent risk of each HTG, since, as has been shown in multiple studies, high fasting and postprandial TG concentrations are an independent risk factor for cardiovascular disease.

Keywords: Hiperquilomicronemia; Hipertrigliceridemia; Hyperchylomycronemia; Hypertrygliceridemia; Monogenic; Monogénica; Poligénica; Polygenic.