NCT04209816

Genetic Pathways Leading to Fatty Liver and Atherogenic Dyslipidemia

Genetic Regulation of Lipid Pathways Contributing to Non-alcoholic Fatty Liver and Atherogenic Dyslipidemia

• Status: Enrolling By Invitation
• Phase: —
• Study type: Observational
• Enrollment: 100 (estimated)
• Sponsor: Marja-Riitta Taskinen · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The aims of the study are: 1. To investigate if carriers of apolipoprotein (apo) CIII loss-of-function (LOF) mutations produce less apo-CIII that results in reduction of large very low-density lipoprotein (VLDL) particle secretion as compared to non-carriers of these variants and compare the results with carriers of apo-CIII gain-of-function (GOF) to elucidate the role of apo-CIII in hepatic lipid metabolism. 2. To study if carriers of the TM6SF2 E167K and PNLPLA3 I148M mutations produce less large VLDL particles to transport fat out of the liver as compared to non-carriers. 3. To test whether the specific mutations in the apo-CIII, TM6SF2 and PNLPLA3 genes are reflected in changes of liver de novo lipogenesis (DNL), liver fat, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), plasma lipid and apolipoprotein kinetics and fasting concentrations in carriers of the TM6SF2 E167K and PNLPLA3 I148M mutations as compared to non-carriers. 4. To study the effects of APOE, angiopoietin (ANGPTL3 and ANGPTL8) or endothelial lipase (LIPG) genotypes on liver fat metabolism, lipid and apolipoprotein metabolism and lipid phenotypes.

Conditions

• Non-alcoholic Fatty Liver
• Atherogenic Dyslipidemia
• Insulin Resistance

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Lipoprotein kinetics	Lipoprotein kinetic apply protocol that endogenously label proteins and fatty acids with stable isotope-labeled amino acid and glycerol tracers. De novo lipogenesis is measured after ingestion of deuterated water to measure newly formed fatty acids in VLDL. Liver fat is measured with magnetic resonance spectroscopy and lipolytic enzymes with heparin test.

Timeline

• Start date: 2019-12-01
• Primary completion: 2024-06-01
• Completion: 2028-12-01
• First posted: 2019-12-24
• Last updated: 2023-09-22

Locations

2 sites across 2 countries: Finland, Sweden