Affinage

APOA5

Apolipoprotein A-V · UniProt Q6Q788

Length
366 aa
Mass
41.2 kDa
Annotated
2026-06-09
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APOA5 encodes a liver-secreted apolipoprotein that lowers plasma triglycerides by sustaining lipoprotein lipase (LPL) activity within the capillaries of oxidative tissues (PMID:33762177, PMID:38880127). Its central mechanism is binding the ANGPTL3/8 complex and suppressing ANGPTL3/8-mediated inhibition of LPL; apoA-V has no direct stimulatory effect on LPL and does not counteract ANGPTL3, ANGPTL4, or ANGPTL4/8 individually (PMID:33762177). This activity is governed by the C-terminal ~35-40 residues, which are required to bind ANGPTL3/8, block ANGPTL3/8-driven detachment of LPL from capillary binding sites, and lower triglycerides in vivo, such that a C-terminal truncation mutant (APOA5Δ40) loses all of these functions (PMID:38625948). Consistent with this, APOA5 deficiency increases ANGPTL3/8-mediated LPL detachment and depletes intracapillary LPL in heart and brown adipose tissue, defects rescued by recombinant APOA5 or by an ANGPTL3/8-specific antibody (PMID:38880127). Beyond LPL anchoring, apoA-V reduces apoC-III content on VLDL to enhance VLDL catabolism (PMID:17438339), and binds LDL-family receptors LRP1, sortilin, and SorLA, with distinct missense and truncation variants separating LPL-activation from receptor-binding functions (PMID:18635818, PMID:23307945). Naturally occurring variants establish causal genotype-phenotype links: S19W impairs signal-peptide-dependent secretion and lowers plasma apoA-V (PMID:15941721, PMID:17936576), the G185C variant introduces a free cysteine that forms aberrant disulfide bonds sequestering apoA-V from lipoproteins (PMID:25127531), and truncations such as Q139X impair VLDL catabolism in carriers (PMID:16200213). APOA5 expression is transcriptionally controlled by thyroid hormone/TR via a DR4 element acting with USF1/USF2 (PMID:15941710) and by CREBH during dietary protein restriction (PMID:30385734), post-transcriptionally repressed by miR-485-5p through a 3'UTR variant (PMID:24387992), and post-translationally degraded via PC7-mediated lysosomal targeting (PMID:31945259).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2005 Medium

    Establishing how a coding polymorphism alters apoA-V abundance addressed whether APOA5 sequence variation acts at the level of protein secretion.

    Evidence Signal-peptide modeling and SP-SEAP fusion secretion assays in HepG2 cells for the S19W variant

    PMID:15941721

    Open questions at the time
    • In vitro secretion reduction not yet confirmed in vivo at this stage
    • Downstream effect on plasma triglycerides not directly measured
  2. 2005 Medium

    Defining the first transcriptional input identified how hepatic APOA5 expression is hormonally controlled.

    Evidence Luciferase reporter and promoter mutagenesis plus T3-treated/hypothyroid rat models mapping a DR4 element and USF1/USF2 synergy

    PMID:15941710

    Open questions at the time
    • Physiological contribution of thyroid regulation to triglyceride control not quantified
    • Single lab
  3. 2005 Medium

    A human truncation pedigree tested whether loss of apoA-V function impairs lipolysis in vivo.

    Evidence Family study with apoB100 kinetics and postheparin LPL activity/mass measurement in Q139X carriers

    PMID:16200213

    Open questions at the time
    • Molecular basis of impaired LPL activity not resolved
    • Truncated protein's altered lipoprotein association mechanistically undefined
  4. 2007 Medium

    An in vivo knock-in confirmed the S19W variant as the causal determinant of reduced plasma apoA-V.

    Evidence Single-copy haplotype insertion at the mouse Hprt locus comparing APOA5*1/*2/*3 plasma apoA-V

    PMID:17936576

    Open questions at the time
    • Does not address triglyceride phenotype mechanism
    • APOA5*2 effect left unexplained at this stage
  5. 2007 Medium

    Defining apoA-V's effect on VLDL composition clarified a receptor/co-factor-independent route to enhanced catabolism.

    Evidence Adenoviral apoA-V gene transfer in APOC3 transgenic mice with lipoprotein fractionation, LCAT and cholesterol efflux assays

    PMID:17438339

    Open questions at the time
    • Mechanism of apoC-III displacement not established
    • HDL maturation effects not linked to a defined receptor pathway
  6. 2008 Medium

    Variant panels separated apoA-V's LPL-activation function from its receptor-binding function.

    Evidence In vitro LPL activity assays with VLDL substrate and LR8/LRP1 binding assays for missense and truncation variants

    PMID:18635818

    Open questions at the time
    • Structural basis of separable functions not defined
    • Physiological weight of receptor binding versus LPL activation unresolved
  7. 2013 Medium

    Mapping multiple disease mutations onto binding partners revealed several functional domains in apoA-V.

    Evidence Recombinant variant proteins assayed for LPL activation, liposome/heparin binding, and LRP1/sortilin/SorLA binding with structural modeling

    PMID:23307945

    Open questions at the time
    • Relative in vivo importance of each domain not tested
    • Single lab
  8. 2014 High

    Identifying aberrant disulfide formation explained how the G185C variant inactivates apoA-V.

    Evidence AAV gene transfer in apoa5-/- mice, nonreducing immunoblot, and IP-LC/MS of human plasma identifying fibronectin and kininogen-1 partners

    PMID:25127531

    Open questions at the time
    • Whether sequestration is reversible or therapeutically targetable unknown
  9. 2014 Medium

    A 3'UTR variant was shown to create a microRNA site, defining a post-transcriptional control mechanism.

    Evidence Luciferase reporter assays in HEK293T and HuH-7 cells with miR-485-5p co-transfection and inhibitor rescue

    PMID:24387992

    Open questions at the time
    • Endogenous magnitude of miR-485-5p regulation in vivo not measured
    • Single lab
  10. 2014 Medium

    Linking apoA-V to tissue lipid uptake placed it in the pathway controlling diet-induced insulin resistance.

    Evidence ASO knockdown in high-fat-diet mice with hyperinsulinemic-euglycemic clamps and tissue DAG/PKC measurements

    PMID:25548259

    Open questions at the time
    • Causality between apoA-V-driven TG delivery and PKC activation correlative
    • Single lab
  11. 2018 Medium

    Establishing CREBH as a regulator connected dietary protein status to APOA5-mediated VLDL clearance.

    Evidence Protein-free diet, Crebh-KO and mTORC1 gain-of-function mice, ASO knockdown, plus a human randomized trial

    PMID:30385734

    Open questions at the time
    • Direct CREBH binding to the APOA5 promoter not shown here
    • Single lab
  12. 2020 Medium

    Identifying PC7-mediated lysosomal degradation defined a post-translational control point for apoA-V abundance.

    Evidence Co-expression in HuH7 cells with lysosomal inhibitors, a PC7 S505E phosphomimetic, and Pcsk7-/- HFD mice

    PMID:31945259

    Open questions at the time
    • Nonenzymatic mechanism of degradation mechanistically unclear
    • Single lab
  13. 2021 High

    Discovering the ANGPTL3/8 interaction resolved the long-sought molecular mechanism of apoA-V's triglyceride-lowering action.

    Evidence IP-MS, biolayer interferometry, and LPL enzymatic/kinetic assays in human serum with positive and negative controls

    PMID:33762177

    Open questions at the time
    • Structure of the apoA-V–ANGPTL3/8 complex not determined
    • Stoichiometry of binding not defined
  14. 2024 High

    Domain mapping and in vivo rescue established that apoA-V's C-terminus is necessary for ANGPTL3/8 binding and capillary LPL retention.

    Evidence Recombinant proteins, APOA5Δ40 truncation, Apoa5-/- mouse rescue, anti-C-terminal antibody blockade, and LPL detachment assays

    PMID:38625948

    Open questions at the time
    • Atomic-level binding interface not solved
    • Whether C-terminus contacts ANGPTL3, ANGPTL8, or both unresolved
  15. 2024 High

    Tissue-level analysis confirmed that apoA-V maintains intracapillary LPL by preventing ANGPTL3/8-mediated detachment.

    Evidence Apoa5-/- mice with recombinant APOA5 and ANGPTL3/8 inhibitory antibody, plus cell-culture LPL detachment assays

    PMID:38880127

    Open questions at the time
    • Tissue selectivity for oxidative organs not fully explained
  16. 2024 Medium

    A hepatocyte-intrinsic role emerged linking apoA-V to NR1D1 and hepatic steatosis independent of plasma lipids.

    Evidence CRISPR ApoA5-/- hamsters with AAV8-NR1D1 liver rescue and mRNA-stability assays in HepG2 cells

    PMID:38505614

    Open questions at the time
    • Mechanism by which apoA-V stabilizes NR1D1 mRNA unknown
    • Intracellular versus secreted apoA-V pool responsible not distinguished

Open questions

Synthesis pass · forward-looking unresolved questions
  • The atomic structure of the apoA-V–ANGPTL3/8 complex and the mechanistic basis of apoA-V's intracellular/hepatic functions remain to be defined.
  • No structural model of the apoA-V–ANGPTL3/8 interface
  • Mechanism coupling secreted apoA-V to hepatic NR1D1 regulation unresolved
  • Stoichiometry and binding interface with LDL-family receptors undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 2 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-382551 Transport of small molecules 2
Partners
ANGPTL3ANGPTL8APOC3LPLLRP1PCSK7SORL1SORT1

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 ApoA5 lowers triglycerides by binding to the ANGPTL3/8 complex in human serum and suppressing ANGPTL3/8-mediated inhibition of lipoprotein lipase (LPL); ApoA5 has no direct stimulatory effect on LPL itself, nor does it suppress LPL inhibition by ANGPTL3, ANGPTL4, or ANGPTL4/8 alone. Immunoprecipitation-MS, Western blotting, biolayer interferometry, functional LPL enzymatic assays, kinetic analyses Journal of lipid research High 33762177
2024 APOA5 C-terminal sequences (last ~35-40 residues) are required for binding ANGPTL3/8, suppressing ANGPTL3/8-mediated inhibition of LPL catalytic activity, blocking ANGPTL3/8-mediated detachment of LPL from capillary binding sites, maintaining intracapillary LPL levels in oxidative tissues, and lowering plasma triglycerides in vivo; a truncation mutant lacking these residues (APOA5Δ40) fails at all these functions. Recombinant protein functional assays, LPL activity assays, Apoa5-/- mouse rescue experiments, anti-APOA5 C-terminal antibody injection in WT mice, cell culture LPL detachment assays Proceedings of the National Academy of Sciences of the United States of America High 38625948
2024 APOA5 deficiency reduces amounts of LPL in capillaries of oxidative tissues (heart, brown adipose tissue) through increased ANGPTL3/8-mediated detachment of LPL from its binding sites; recombinant APOA5 normalizes both intracapillary LPL levels and plasma triglycerides in Apoa5-/- mice, and an ANGPTL3/8-specific inhibitory antibody phenocopies APOA5 function. Apoa5-/- mouse model, recombinant APOA5 administration, ANGPTL3/8 inhibitory antibody treatment, cell culture LPL binding/detachment assays Journal of lipid research High 38880127
2005 The APOA5 S19W (c.56C>G) polymorphism impairs secretion of apoA-V: molecular modeling predicts increased membrane insertion angle for Trp-19 signal peptide, and an in vitro secretion assay using SP-SEAP fusion proteins in HepG2 cells showed ~50% reduction in secretion of the Trp-19 encoded signal peptide compared to Ser-19. Molecular modeling of signal peptide, SP-SEAP fusion protein secretion assay in HepG2 cells, in vitro transcription/translation assay, primer extension inhibition assay, luciferase reporter assay The Journal of biological chemistry Medium 15941721
2007 The S19W (APOA5*3) haplotype-defining polymorphism is functionally responsible for reduced plasma apoA-V levels: knock-in of the single APOA5*3 allele (19W) at the mouse Hprt locus resulted in three-fold lower human plasma ApoA-V levels compared to common APOA5*1 haplotype, while APOA5*2 showed no difference in plasma apoA-V. Targeted single-copy haplotype insertion at Hprt locus in mice, plasma apoA-V measurement Genomics Medium 17936576
2005 APOA5 Q139X truncation mutation impairs VLDL catabolism and reduces lipoprotein lipase activity and mass in carriers; the truncated apoA-V protein shows altered association with plasma lipoprotein fractions compared to wild-type apoA-V. APOB100 kinetic studies revealed major impairment of VLDL catabolism in dyslipidemic Q139X carriers. Family/pedigree study, ultracentrifugation lipoprotein fractionation, APOB100 kinetic studies, postheparin LPL activity and mass measurement The Journal of clinical investigation Medium 16200213
2008 Specific APOA5 missense variants (E255G, G185C, H321L) reduce LPL activation using VLDL as substrate in vitro (by 23-36%), while truncation variants (Q139X, Q148X) and G271C show no significant reduction in LPL activity but abolish binding to LDL-family receptors LR8 and LRP1. In vitro LPL activity assay using VLDL substrate, receptor-binding assay to LR8 and LRP1 with recombinant apoA-V variants Arteriosclerosis, thrombosis, and vascular biology Medium 18635818
2013 Three APOA5 mutations [p.(Ser232_Leu235)del, p.Leu253Pro, p.Asp332ValfsX4] impair LPL activation in vitro; recombinant mutant apoA-V variants show defective interactions with liposomes, heparin, LRP1, sortilin, and SorLA/LR11 compared to wild-type, indicating multiple functional domains are affected. Recombinant protein expression and purification, LPL activation assay, liposome binding, heparin binding, LRP1/sortilin/SorLA receptor binding assays, 3D structural modeling Journal of lipid research Medium 23307945
2014 The APOA5 c.553G>T (rs2075291, p.Gly185Cys) variant introduces a free cysteine that forms aberrant hetero-disulfide bonds with plasma proteins (fibronectin, kininogen-1, and others), sequestering >50% of G162C apoA-V in the lipoprotein-free fraction and compromising its lipoprotein-binding and triglyceride-modulating functions. AAV2/8-mediated gene transfer in apoa5-/- mice, plasma fractionation, nonreducing SDS-PAGE immunoblot, immunoprecipitation followed by LC/MS of human plasma from homozygous subjects Arteriosclerosis, thrombosis, and vascular biology High 25127531
2005 Thyroid hormone T3 directly regulates APOA5 expression in hepatocytes via a DR4 thyroid hormone response element in the APOA5 promoter; T3-activated thyroid receptor (TR) acts synergistically with USF1 and USF2 via an adjacent E-box motif to activate APOA5 promoter in a ligand-dependent manner. Luciferase reporter assays in hepatocytes, APOA5 mRNA/protein measurement in T3-treated and hypothyroid rats, TRbeta-selective agonist treatment, promoter deletion/mutation analysis The Journal of biological chemistry Medium 15941710
2014 The APOA5 3'UTR variant c.*158C (rs2266788) creates a functional binding site for liver-expressed miR-485-5p, leading to post-transcriptional downregulation of APOA5 mRNA; reporter assays and miR-485-5p inhibitor rescue confirmed this mechanism as a basis for the hypertriglyceridemic effect of the APOA5*2 haplotype. Luciferase reporter assay with APOA5 3'UTR in HEK293T and HuH-7 cells, miR-485-5p precursor co-transfection, miR-485-5p inhibitor rescue experiment, bioinformatics American journal of human genetics Medium 24387992
2018 APOA5 expression is regulated by the transcription factor CREBH in response to dietary protein restriction; PR stimulates VLDL-TG clearance by increasing VLDL-bound APOA5 expression, an effect abrogated by constitutive hepatic mTORC1 activation. This CREBH-APOA5 axis was conserved in a human clinical trial showing reduced VLDL particle number and increased VLDL-bound APOA5 upon protein restriction. Protein-free diet mouse model, Crebh-knockout mice, mTORC1 gain-of-function mice, ASO-mediated knockdown, VLDL-TG clearance assays, randomized controlled clinical trial JCI insight Medium 30385734
2007 ApoA-V reduces apoC-III content in VLDL, resulting in enhanced VLDL catabolism without altering VLDL production; apoA-V also enriches HDL with apoA-I and apoE, enhances LCAT activity, and increases cholesterol efflux, promoting HDL maturation in APOC3 transgenic mice. Adenovirus-mediated apoA-V gene transfer into APOC3 transgenic mice, plasma TG/cholesterol measurement, lipoprotein fractionation, LCAT activity assay, cholesterol efflux assay Journal of lipid research Medium 17438339
2014 ApoA5 knockdown in high-fat-diet mice (via ASO reducing hepatic ApoA5 by 60-70%) reduces TG uptake in liver and skeletal muscle, decreasing diacylglycerol content and DAG-mediated activation of PKCε (liver) and PKCθ (muscle), thereby protecting against diet-induced insulin resistance as assessed by hyperinsulinemic-euglycemic clamps. Antisense oligonucleotide knockdown in mice, VLDL-TG clearance assays, hyperinsulinemic-euglycemic clamp, PKC activity measurement, AKT2 phosphorylation assay, tissue TG/DAG measurement Journal of lipid research Medium 25548259
2020 Proprotein convertase PC7 (PCSK7) binds to apoA-V and promotes its degradation in acidic lysosomes in a nonenzymatic fashion (inhibited by bafilomycin A1, chloroquine, NH4Cl); phosphorylation of PC7 at Ser505 by Fam20C reduces apoA-V degradation. In Pcsk7-/- mice on high-fat diet, plasma apoA-V levels and adipocyte LPL activity are increased. Co-expression in HuH7 cells with bafilomycin A1/chloroquine/NH4Cl inhibition, PC7 phosphomimetic mutant (S505E) co-expression, Pcsk7-/- mouse model on HFD, adipocyte LPL activity measurement The FEBS journal Medium 31945259
2024 ApoA5 deficiency in CRISPR/Cas9-edited hamsters causes hepatic steatosis associated with reduced NR1D1 mRNA stability and protein levels; AAV8-mediated overexpression of NR1D1 in ApoA5-/- hamster livers ameliorated fatty liver without correcting plasma lipid levels, indicating a direct hepatic role for ApoA5 in regulating NR1D1. CRISPR/Cas9 ApoA5-/- hamster model, HFD challenge, AAV8-NR1D1 liver overexpression, mRNA stability assay in HepG2 cells, UCP1 activation experiments Theranostics Medium 38505614

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature 532 25487149
2012 Mutations in LPL, APOC2, APOA5, GPIHBP1 and LMF1 in patients with severe hypertriglyceridaemia. Journal of internal medicine 204 22239554
2004 Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study. Journal of lipid research 139 15342688
2005 Apoa5 Q139X truncation predisposes to late-onset hyperchylomicronemia due to lipoprotein lipase impairment. The Journal of clinical investigation 130 16200213
2003 The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore. Journal of lipid research 123 12951359
2003 Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges. Biochimica et biophysica acta 105 12697303
2003 Genetic analysis of a polymorphism in the human apoA-V gene: effect on plasma lipids. Journal of lipid research 101 12671030
2005 Determination of the functionality of common APOA5 polymorphisms. The Journal of biological chemistry 100 15941721
2004 APOA5 gene variants, lipoprotein particle distribution, and progression of coronary heart disease: results from the LOCAT study. Journal of lipid research 92 14729863
2006 APOA5 and triglyceride metabolism, lesson from human APOA5 deficiency. Current opinion in lipidology 76 16531747
2007 APOA5 gene variation modulates the effects of dietary fat intake on body mass index and obesity risk in the Framingham Heart Study. Journal of molecular medicine (Berlin, Germany) 74 17211608
2003 APOA5-1131T>C polymorphism is associated with triglyceride levels in Chinese men. Clinical genetics 73 12752569
2021 ApoA5 lowers triglyceride levels via suppression of ANGPTL3/8-mediated LPL inhibition. Journal of lipid research 72 33762177
2004 APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease. Atherosclerosis 66 15306190
2006 The -1131 T>C and S19W APOA5 gene polymorphisms are associated with high levels of triglycerides and apolipoprotein C-III, but not with coronary artery disease: an angiographic study. Atherosclerosis 62 16682041
2007 APOA5 variants and metabolic syndrome in Caucasians. Journal of lipid research 61 17768309
2014 A functional variant in APOA5/A4/C3/A1 gene cluster contributes to elevated triglycerides and severity of CAD by interfering with microRNA 3201 binding efficiency. Journal of the American College of Cardiology 58 25034063
2012 The paradox of ApoA5 modulation of triglycerides: evidence from clinical and basic research. Clinical biochemistry 57 23000317
2011 APOA5 gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerides in a Mediterranean population. The Journal of nutrition 56 21209257
2017 The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis. Atherosclerosis 55 28865324
2006 Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study. Journal of lipid research 55 16474174
2006 Plasma apoAV levels are markedly elevated in severe hypertriglyceridemia and positively correlated with the APOA5 S19W polymorphism. Atherosclerosis 55 16777114
2015 Interaction of dietary fat intake with APOA2, APOA5 and LEPR polymorphisms and its relationship with obesity and dyslipidemia in young subjects. Lipids in health and disease 54 26365669
2005 Thyroid hormone regulates the hypotriglyceridemic gene APOA5. The Journal of biological chemistry 54 15941710
2014 An APOA5 3' UTR variant associated with plasma triglycerides triggers APOA5 downregulation by creating a functional miR-485-5p binding site. American journal of human genetics 52 24387992
2014 ApoA5 knockdown improves whole-body insulin sensitivity in high-fat-fed mice by reducing ectopic lipid content. Journal of lipid research 52 25548259
2008 Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding. Arteriosclerosis, thrombosis, and vascular biology 52 18635818
2017 Update on APOA5 Genetics: Toward a Better Understanding of Its Physiological Impact. Current atherosclerosis reports 49 28500476
2016 Association and interaction of APOA5, BUD13, CETP, LIPA and health-related behavior with metabolic syndrome in a Taiwanese population. Scientific reports 49 27827461
2008 APOA5 genetic variants are markers for classic hyperlipoproteinemia phenotypes and hypertriglyceridemia. Nature clinical practice. Cardiovascular medicine 48 18779834
2006 Evidence for a complex relationship between apoA-V and apoC-III in patients with severe hypertriglyceridemia. Journal of lipid research 48 16861622
2004 APOA5 polymorphisms influence plasma triglycerides in young, healthy African Americans and whites of the CARDIA Study. Journal of lipid research 48 15604515
2008 The apolipoprotein A5 -1131T>C promoter polymorphism in Koreans: association with plasma APOA5 and serum triglyceride concentrations, LDL particle size and coronary artery disease. Clinica chimica acta; international journal of clinical chemistry 47 19159622
2007 Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice. Journal of lipid research 47 17438339
2012 APOA5 genotype modulates 2-y changes in lipid profile in response to weight-loss diet intervention: the Pounds Lost Trial. The American journal of clinical nutrition 46 22914552
2008 Hypertriglyceridaemia and low plasma HDL in a patient with apolipoprotein A-V deficiency due to a novel mutation in the APOA5 gene. Journal of internal medicine 46 18324930
2008 Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states. The American journal of clinical nutrition 45 19056598
2010 Strong association of the APOA5-1131T>C gene variant and early-onset acute myocardial infarction. Atherosclerosis 44 21130994
2006 Impact of APOA5/A4/C3 genetic polymorphisms on lipid variables and cardiovascular disease risk in French men. International journal of cardiology 44 16321685
2013 Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia. Journal of lipid research 41 23307945
2013 Effects of APOA5 -1131T>C (rs662799) on fasting plasma lipids and risk of metabolic syndrome: evidence from a case-control study in China and a meta-analysis. PloS one 41 23468858
2006 Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans. BMC medical genetics 41 17032446
2005 SNPs at the APOA5 gene account for the strong association with hypertriglyceridaemia at the APOA5/A4/C3/A1 locus on chromosome 11q23 in the Northern Irish population. Atherosclerosis 41 16125709
2018 Dietary protein restriction reduces circulating VLDL triglyceride levels via CREBH-APOA5-dependent and -independent mechanisms. JCI insight 39 30385734
2011 Variants in the APOA5 gene region and the response to combination therapy with statins and fenofibric acid in a randomized clinical trial of individuals with mixed dyslipidemia. Atherosclerosis 39 21889769
2009 Genetic association and interaction analysis of USF1 and APOA5 on lipid levels and atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 39 19910639
2006 Protease inhibitor-associated dyslipidemia in HIV-infected patients is strongly influenced by the APOA5-1131T->C gene variation. Clinical chemistry 39 16887900
2016 Interactions of Environmental Factors and APOA1-APOC3-APOA4-APOA5 Gene Cluster Gene Polymorphisms with Metabolic Syndrome. PloS one 34 26824674
2008 Gender-modulated impact of apolipoprotein A5 gene (APOA5) -1131T>C and c.56C>G polymorphisms on lipids, dyslipidemia and metabolic syndrome in Turkish adults. Clinical chemistry and laboratory medicine 34 18601598
2006 The effect of APOA5 and APOC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbeans with type 2 diabetes. Biochimica et biophysica acta 33 17197160
2006 Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study. Metabolism: clinical and experimental 31 17142127
2008 Influence of apoA-V gene variants on postprandial triglyceride metabolism: impact of gender. Journal of lipid research 30 18263854
2007 Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia. The pharmacogenomics journal 30 17726453
2007 Rare APOA5 mutations--clinical consequences, metabolic and functional effects: an ENID review. Atherosclerosis 29 17222847
2014 Triglyceride-raising APOA5 genetic variants are associated with obesity and non-HDL-C in Chinese children and adolescents. Lipids in health and disease 28 24903888
2005 Polymorphisms in the apolipoprotein A5 (APOA5) gene and type III hyperlipidemia. Clinical genetics 28 16143024
2015 APOA5 variants predispose hyperlipidemic patients to atherogenic dyslipidemia and subclinical atherosclerosis. Atherosclerosis 27 25770687
2014 Consumption of whole grains and legumes modulates the genetic effect of the APOA5 -1131C variant on changes in triglyceride and apolipoprotein A-V concentrations in patients with impaired fasting glucose or newly diagnosed type 2 diabetes. Trials 27 24690159
2013 Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults. Lipids in health and disease 27 23656756
2008 The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits. Diabetologia 27 19018513
2014 Association of USF1 and APOA5 polymorphisms with familial combined hyperlipidemia in an Italian population. Molecular and cellular probes 25 25308402
2012 Associations of apolipoprotein A5 (APOA5), glucokinase (GCK) and glucokinase regulatory protein (GCKR) polymorphisms and lifestyle factors with the risk of dyslipidemia and dysglycemia in Japanese - a cross-sectional data from the J-MICC Study. Endocrine journal 25 22517333
2006 Comparison of low-fat meal and high-fat meal on postprandial lipemic response in non-obese men according to the -1131T>C polymorphism of the apolipoprotein A5 (APOA5) gene (randomized cross-over design). Journal of the American College of Nutrition 25 16943456
2011 Association of PON1 and APOA5 gene polymorphisms in a cohort of Indian patients having coronary artery disease with and without type 2 diabetes. Genetic testing and molecular biomarkers 24 21438666
2014 Association of APOA5 rs662799 and rs3135506 polymorphisms with arterial hypertension in Moroccan patients. Lipids in health and disease 23 24684850
2008 Association of APOA5 -1131T>C and S19W gene polymorphisms with both mild hypertriglyceridemia and hyperchylomicronemia in type 2 diabetic patients. Clinica chimica acta; international journal of clinical chemistry 23 18468520
2008 Determinants of plasma apolipoprotein A-V and APOA5 gene transcripts in humans. Journal of internal medicine 22 18537870
2010 The influence of the S19W SNP of the APOA5 gene on triglyceride levels in southern Brazil: interactions with the APOE gene, sex and menopause status. Nutrition, metabolism, and cardiovascular diseases : NMCD 21 20304614
2009 The -1131T>C SNP of the APOA5 gene modulates response to fenofibrate treatment in patients with the metabolic syndrome: a postprandial study. Atherosclerosis 21 19344899
2009 Modulation of phenotypic expression of APOA5 Q97X and L242P mutations. Atherosclerosis 21 19447388
2007 In vivo characterization of human APOA5 haplotypes. Genomics 21 17936576
2018 Effects of polymorphisms in APOA5 on the plasma levels of triglycerides and risk of coronary heart disease in Jilin, northeast China: a case-control study. BMJ open 20 29866721
2015 Effects of Polymorphisms in APOA4-APOA5-ZNF259-BUD13 Gene Cluster on Plasma Levels of Triglycerides and Risk of Coronary Heart Disease in a Chinese Han Population. PloS one 20 26397108
2014 Rs964184 (APOA5-A4-C3-A1) is related to elevated plasma triglyceride levels, but not to an increased risk for vascular events in patients with clinically manifest vascular disease. PloS one 20 24979386
2010 APOA5-1131T>C genotype effects on apolipoprotein A5 and triglyceride levels in response to dietary intervention and regular exercise (DIRE) in hypertriglyceridemic subjects. Atherosclerosis 20 20392444
2010 A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese. European journal of human genetics : EJHG 20 20571505
2014 Aberrant hetero-disulfide bond formation by the hypertriglyceridemia-associated p.Gly185Cys APOA5 variant (rs2075291). Arteriosclerosis, thrombosis, and vascular biology 19 25127531
2014 Influences of APOA5 variants on plasma triglyceride levels in Uyghur population. PloS one 19 25313938
2012 Vitamin D dependent effects of APOA5 polymorphisms on HDL cholesterol. Atherosclerosis 19 22425169
2011 Resequencing the apolipoprotein A5 (APOA5) gene in patients with various forms of hypertriglyceridemia. Atherosclerosis 19 21993410
2010 The apolipoprotein A5 (APOA5) gene predisposes Caucasian children to elevated triglycerides and vitamin E (Four Provinces Study). Atherosclerosis 19 20688329
2009 Association of APOA5 and APOC3 gene polymorphisms with plasma apolipoprotein A5 level in patients with metabolic syndrome. Biochemical and biophysical research communications 19 19932084
2008 Interaction between APOA5 -1131T>C and APOE polymorphisms and their association with severe hypertriglyceridemia. Clinica chimica acta; international journal of clinical chemistry 19 18549811
2008 Changes of plasma lipids during weight reduction in females depends on APOA5 variants. Annals of nutrition & metabolism 19 18946207
2020 Proprotein convertase 7 (PCSK7) reduces apoA-V levels. The FEBS journal 18 31945259
2020 Gene-environment interaction between APOA5 c.553G>T and pregnancy in hypertriglyceridemia-induced acute pancreatitis. Journal of clinical lipidology 18 32561169
2017 Estrogen lowers triglyceride via regulating hepatic APOA5 expression. Lipids in health and disease 18 28376804
2016 APOA5 and APOA1 polymorphisms are associated with triglyceride levels in Mexican children. Pediatric obesity 18 27171122
2014 Static and turnover kinetic measurement of protein biomarkers involved in triglyceride metabolism including apoB48 and apoA5 by LC/MS/MS. Journal of lipid research 18 24694356
2011 Two novel rare variants of APOA5 gene found in subjects with severe hypertriglyceridemia. Clinica chimica acta; international journal of clinical chemistry 18 21846464
2006 Haplotype analyses of the APOA5 gene in patients with familial combined hyperlipidemia. Biochimica et biophysica acta 18 17157483
2015 Relationship of the APOA5/A4/C3/A1 gene cluster and APOB gene polymorphisms with dyslipidemia. Genetics and molecular research : GMR 17 26345861
2024 Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters. Theranostics 16 38505614
2024 APOA5 deficiency causes hypertriglyceridemia by reducing amounts of lipoprotein lipase in capillaries. Journal of lipid research 16 38880127
2024 Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3/8 activity. Proceedings of the National Academy of Sciences of the United States of America 15 38625948
2019 Association of BUD13-ZNF259-APOA5-APOA1-SIK3 cluster polymorphism in 11q23.3 and structure of APOA5 with increased plasma triglyceride levels in a Korean population. Scientific reports 15 31165758
2017 A promoter variant of the APOA5 gene increases atherogenic LDL levels and arterial stiffness in hypertriglyceridemic patients. PloS one 15 29211729
2011 Relationship of APOA5, PPARγ and HL gene variants with serial changes in childhood body mass index and coronary artery disease risk factors in young adulthood. Lipids in health and disease 15 21548985
2016 APOA5 genetic and epigenetic variability jointly regulate circulating triacylglycerol levels. Clinical science (London, England : 1979) 14 27613158
2009 Gene-gene interaction between APOA5 and USF1: two candidate genes for the metabolic syndrome. Obesity facts 14 20054229

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