Genetics
Review links apoB signal-peptide and CETP B1B1 combination to lower VLDL apoB secretion in obese men (Curr Opin Lipidol 2010)
Original title: Genetic determinants of apolipoprotein B-100 kinetics
This review of stable-isotope tracer studies on apolipoprotein B-100 (apoB) kinetics reports that, in obese men, the allelic combination of the apoB signal-peptide variant SP24 with CETP B1B1 is independently associated with lower VLDL apoB secretion. Other genetic determinants covered include microsomal triglyceride transfer protein -493G/T, ABCG8 and NPC1L1 mutations affecting VLDL/LDL apoB production and catabolism, and lipase and transfer-protein mutations, including in CETP itself, that alter functional activity and impact VLDL and LDL kinetics. The review concludes that mutations regulating intrahepatic apoB assembly and lipid substrate availability shape VLDL apoB secretion, with lipoprotein tracer studies offering functional insight into these genetic effects.
Original abstract
Purpose Of Review: We review stable isotope tracer studies of apolipoprotein B-100 (apoB) kinetics concerning genetic polymorphisms and mutations that affect human lipoprotein metabolism.
Recent Findings: In obese men, the allelic combination of the apoB signal peptide, SP24, and cholesteryl ester transfer protein, CETP B1B1, is independently associated with lower VLDL apoB secretion. Microsomal triglyceride transfer protein -493G/T carriers have reduced IDL apoB and LDL apoB production as compared with controls. Mutations in cholesterol transporters (ATP-binding cassette transporter G8 and Niemann-Pick C1 Like 1) are associated with reduced VLDL apoB secretion and increased LDL apoB production and catabolism. The ATP-binding cassette transporter G8 400K variant is a significant, independent predictor of VLDL apoB secretion. Mutations in lipases (lipoprotein lipase and hepatic lipase) and transfer proteins (lecithin-cholesterol acyltransferase and cholesteryl ester transfer protein) alter their functional activity, which impact on VLDL and LDL kinetics.
Summary: Mutations in genes that regulate intrahepatic apoB assembly and lipid substrate availability to the liver impact on VLDL apoB secretion. Lipoprotein tracer studies can provide functional insight into the potential impact of genetic polymorphisms in regulating apoB metabolism in humans.
geneticsLDL and apoBmechanisms
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.