Cross-sectional study
ANGPTL3 Deficiency and Risk of Hepatic Steatosis
- Cross-sectional genetic study with Mendelian randomisation analysis
- 2 previously characterized cohorts (Campodimele, Italy; St. Louis, MO)
- Mendelian randomization in UK Biobank
Authors' conclusion
ANGPTL3 deficiency related to LoF mutations in ANGPTL3, as well as genetically determined reduction of plasma ANGPTL3 levels, is not associated with hepatic steatosis.
Study context
- Population
- Participants with ANGPTL3 loss-of-function (LoF) mutations and wild-type participants from 2 cohorts (Campodimele, Italy; St. Louis, MO)
- Participants
- 6 / 32 / 92
- Exposure
- ANGPTL3 deficiency vs wild-type
- Complete deficiencyn = 6
- Partial deficiencyn = 32
- Wild-type (WT)n = 92reference
- Outcome
- Hepatic fat fraction by magnetic resonance spectroscopy and MRI proton density fat fraction
Main finding
As reported in the abstract
Hepatic fat
- No significant difference in hepatic fat or severity of hepatic steatosis vs WT
- P > 0.05
Observational data: associations, not effects.
Further findings
Total cholesterol
Plasma TG
- Total cholesterol: P<0.05 for both deficiency groups vs WT
- Plasma TG: P<0.05 for both deficiency groups vs WT
Extrahepatic fat distribution
- ANGPTL3 deficiency did not alter the distribution of extrahepatic fat
Mendelian randomization, UK Biobank (n=36 703): genetically determined ANGPTL3 levels
- Causally associated with LDL-C
- P = 1.7×10-17
- Causally associated with TG
- P = 3.2×10-18
- Not associated with hepatic fat
- P = 0.22
Original publication
ANGPTL3 Deficiency and Risk of Hepatic Steatosis. Circulation. Published 15 September 2023. doi:10.1161/circulationaha.123.065866
Summarised from the published abstract; every number is checked against it