Allelic and phenotypic spectrum of plasma triglycerides

The genetic underpinnings of both normal and pathological variation in plasma triglyceride (TG) concentration are relatively well understood compared to many other complex metabolic traits. For instance, genome-wide association studies (GWAS) have revealed 32 common variants that are associated with plasma TG concentrations in healthy epidemiologic populations. Furthermore, GWAS in clinically ascertained hypertriglyceridemia (HTG) patients have shown that almost all of the same TG-raising alleles from epidemiologic samples are also associated with HTG disease status, and that greater accumulation of these alleles reflects the severity of the HTG phenotype. Finally, comprehensive resequencing studies show a burden of rare variants in some of these same genes – namely in LPL, GCKR, APOB and APOA5 – in HTG patients compared to normolipidemic controls. A more complete understanding of the genes and genetic variants associated with plasma TG concentration will enrich our understanding of the molecular pathways that modulate plasma TG metabolism, which may translate into clinical benefit. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.