The Genetic Basis of Hypertriglyceridemia

Figures

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  Fig. 1. Genetic mechanisms implicated in hypertriglyceridemia. A Dietary triglycerides are absorbed from the small intestine and enter the circulation packed in chylomicrons. The liver synthesizes triglycerides de novo from free fatty acids and packs them into very low-density lipoproteins (VLDLs). B The chylomicrons and VLDL deliver the triglycerides to adipose tissue, skeletal muscle, and cardiac muscle where lipoprotein lipase (LPL) cleaves triglycerides. C In the adipose tissue, triglycerides are stored within adipocyte lipid droplets. D The breakdown of triglycerides by LPL turns chylomicrons and VLDL gradually into remnant lipoproteins (RPLs). E Remnant lipoproteins are cleared by the liver via ApoE that facilitates binding of RLP to the LDL receptor (LDLR) on the liver. When RPL levels are high, RLP clearance by the liver reaches saturation and RLP molecules accumulate in plasma. Figure icons were created with BioRender.com

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  Fig. 2. The genetic architecture of hypertriglyceridemia. In very rare, monogenic disorders, a single recessive variant may cause a severe hypertriglyceridemia (red box). Rare heterozygous variants with large effects may contribute to the clustering of certain hypertriglyceridemia phenotypes in families (yellow box). In most cases of hypertriglyceridemia, the genetic basis is highly polygenic, driven by the cumulative effect of multiple common and rare variants with modest effect sizes (green box)