Multiple microRNA regulation of lipoprotein lipase gene abolished by 3'UTR polymorphisms in a triglyceride-lowering haplotype harboring p.Ser474Ter.

Background: Lipoprotein lipase (LPL) is a key enzyme in triglyceride (TG) metabolism. LPL gene single nucleotide polymorphisms (SNPs) are associated with TG concentrations however the functionality of many of these SNPs remains poorly understood. MicroRNAs (miR) exert post-transcriptional down-regulation and their target sequence on the 3'UTR may be altered by SNPs.

Post-heparin LPL activity measurement using VLDL as a substrate: a new robust method for routine assessment of plasma triglyceride lipolysis defects.

Background: Determination of lipoprotein lipase (LPL) activity is important for hyperchylomicronemia diagnosis, but remains both unreliable and cumbersome with current methods. Consequently by using human VLDL as substrate we developed a new LPL assay which does not require sonication, radioactive or fluorescent particles.

Methods: Post-heparin plasma was added to the VLDL substrate prepared by ultracentrifugation of heat inactivated normolipidemic human serums, diluted in buffer, pH 8.

Post-heparin LPL activity measurement using VLDL as a substrate: a new robust method for routine assessment of plasma triglyceride lipolysis defects.

Background: Determination of lipoprotein lipase (LPL) activity is important for hyperchylomicronemia diagnosis, but remains both unreliable and cumbersome with current methods. Consequently by using human VLDL as substrate we developed a new LPL assay which does not require sonication, radioactive or fluorescent particles.

Methods: Post-heparin plasma was added to the VLDL substrate prepared by ultracentrifugation of heat inactivated normolipidemic human serums, diluted in buffer, pH 8.

An APOA5 3' UTR variant associated with plasma triglycerides triggers APOA5 downregulation by creating a functional miR-485-5p binding site.

APOA5 c.*158C>T (rs2266788), located in the 3' UTR, belongs to APOA5 haplotype 2 (APOA5*2), which is strongly associated with plasma triglyceride levels and modulates the occurrence of both moderate and severe hypertriglyceridemia. Individuals with APOA5*2 display reduced APOA5 expression at the posttranscriptional level.

GPIHBP1 C89F neomutation and hydrophobic C-terminal domain G175R mutation in two pedigrees with severe hyperchylomicronemia.

Context: GPIHBP1 is a new endothelial binding site for lipoprotein lipase (LPL), the key enzyme for intravascular lipolysis of triglyceride-rich lipoproteins (TGRL). We have identified two new missense mutations of the GPIHBP1 gene, C89F and G175R, by systematic sequencing in a cohort of 376 hyperchylomicronemic patients without mutations on the LPL, APOC2, or APOA5 gene.

Objective: Phenotypic expression and functional consequences of these two mutations were studied.

Combination of circulating antilipoprotein lipase (Anti-LPL) antibody and heterozygous S172 fsX179 mutation of LPL gene leading to chronic hyperchylomicronemia.

Context: Sporadic hyperchylomicronemia (type V hyperlipoproteinemia) results from complex interactions between genetic and environmental factors that often remain unknown.

Design: Upon investigation of a patient suffering from recurrent hypertriglyceridemic pancreatitis without family history or conventional secondary cause of dyslipidemia, we identified a previously unreported nonsense heterozygous lipoprotein lipase (LPL) gene mutation S172fsX179 associated with an antihuman LPL IgG.

Results: This autoantibody partially inhibited wild-type LPL activity in vitro.