Resolving the Longitudinal Triglyceride Phenotype of Heterozygous LPL and Apo A-V Deficiency

Shehan D. Perera, The University of Western Ontario

Abstract

Hypertriglyceridemia (HTG) is a risk factor for cardiovascular disease. However, only the triglyceride (TG) phenotype produced by biallelic loss-of-function (LOF) variants in the canonical TG metabolism genes is well understood. The TG phenotype produced by monoallelic LOF variants is poorly understood. We aimed to evaluate the TG phenotype associated with monoallelic LOF variants in the canonical TG metabolism genes.

Next-generation sequencing panel was employed to identify patients heterozygous for LOF variants in two of the canonical TG metabolism genes LPL and APOA5, followed by chart review to determine baseline and longitudinal TG phenotype in these patients.

My findings suggest that heterozygosity for LOF variants in these genes is associated with highly variable TG phenotype, both at baseline and longitudinally. Thus, my findings describe a unique, previously underappreciated TG phenotype and identification of these variants may serve as an early warning to physicians regarding difficulty in treating HTG in these patients.