Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL
Open accessAbstract
Resequencing genes provides the opportunity to assess the full spectrum of variants that influence complex traits. Here we report the first application of resequencing to a large population (n = 3,551) to examine the role of the adipokine ANGPTL4 in lipid metabolism. Nonsynonymous variants in ANGPTL4 were more prevalent in individuals with triglyceride levels in the lowest quartile than in individuals with levels in the highest quartile (P = 0.016). One variant (E40K), present in approximately 3% of European Americans, was associated with significantly lower plasma levels of triglyceride and higher levels of high-density lipoprotein cholesterol in European Americans from the Atherosclerosis Risk in Communities Study and in Danes from the Copenhagen City Heart Study. The ratio of nonsynonymous to synonymous variants was higher in European Americans than in African Americans (4:1 versus 1.3:1), suggesting population-specific relaxation of purifying selection. Thus, resequencing of ANGPTL4 in a multiethnic population allowed analysis of the phenotypic effects of both rare and common variants while taking advantage of genetic variation arising from ethnic differences in population history.
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ANGPTL4 regulates LPL activity, analogous to ANGPTL3, but its mechanism is incompletely defined.
“Finally, angiopoietin-like protein 4 (ANGPTL4) regulates LPL activity, analogous to ANGPTL3, but its mechanism is incompletely defined.91,97,98”
From Clinical review on triglycerides (2020) · cites this paper as [97]
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- Authors
- Romeo, S., Pennacchio, L. A., Fu, Y., Boerwinkle, E., Tybjaerg-Hansen, A., Hobbs, H. H., & Cohen, J. C.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Lawrence Berkeley National Laboratory (US)
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- Hobbs, Helen H
- Cohen, Jonathan C
- Venue
- Nature Genetics
- Published
- 2007-02-25
- Volume
- 39
- Issue
- 4
- Pages
- 513-516
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2762948
- OpenAlex
- W2146750742
- Cited by
- 511
- References
- 23
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 6 · 2023: 11 · 2022: 10 · 2021: 17 · 2020: 13 · 2019: 23 · 2018: 18 · 2017: 15 · 2016: 24 · 2015: 19 · 2014: 36 · 2013: 35 · 2012: 50
- FWCI
- 42.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Joint Genome Institute
- National Heart, Lung, and Blood Institute (HL-066681, U01HL066681, RL1HL092550)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- ANGPTL4, triglycerides, HDL cholesterol, lipid metabolism, non-synonymous mutations, purifying selection, genetic differentiation, European Americans, African Americans, genetic variants, Atherosclerosis Risk in Communities Study, Copenhagen City Heart Study
- MeSH terms
- Angiopoietin-Like Protein 4, Adult, Black or African American, Energy Metabolism, Gene Frequency, Hispanic or Latino, Humans, Genetic Linkage, Cholesterol, HDL, Middle Aged, Phenotype, Texas, Triglycerides, Cohort Studies, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Intercellular Signaling Peptides and Proteins, Angiopoietins, White People
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