HDL biology
Homozygous B4GALT1 mutations cause CETP hypoglycosylation and reduced activity, yielding larger HDL particles (J Inherit Metab Dis 2020)
Original title: Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations
Studying three patients with B4GALT1-CDG, a congenital disorder of glycosylation caused by mutations in B4GALT1 with defective N-linked glycosylation, and 11 age- and gender-matched healthy controls, plasma cholesteryl ester transfer protein (CETP) glyco-isoforms were assessed by isoelectric focusing with western blot alongside CETP activity. B4GALT1-CDG patients had significantly lower non-HDL cholesterol and total cholesterol to HDL cholesterol ratio than controls, along with larger HDL particles. Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients than in matched controls, indicating that protein galactosylation regulates plasma HDL and LDL homeostasis and that the larger HDL particles seen in these patients likely result from their hypogalactosylated, hypoactive CETP.
Original abstract
The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent. We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation. We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls. B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles. Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls. Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis. The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL. Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.