Affinage

APOA5

Apolipoprotein A-V · UniProt Q6Q788

Length
366 aa
Mass
41.2 kDa
Annotated
2026-04-28
100 papers in source corpus 19 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APOA5 encodes a liver-secreted apolipoprotein that is a central regulator of plasma triglyceride homeostasis, acting through multiple convergent mechanisms to promote triglyceride-rich lipoprotein (TRL) catabolism and clearance. ApoA5 lowers triglycerides primarily by binding and suppressing the ANGPTL3/8 complex, thereby relieving its inhibition of lipoprotein lipase (LPL), without directly activating LPL itself (PMID:33762177); it also accelerates VLDL catabolism and facilitates receptor-mediated TRL uptake via LRP1, sortilin, and SorLA, functions that depend on C-terminal lipid-binding domains abolished by truncation or missense mutations (PMID:23307945, PMID:18635818). Transcriptional regulation of APOA5 is mediated by thyroid hormone acting through a DR4 element with USF1/USF2 cooperation (PMID:15941710) and by CREBH under protein restriction conditions gated by mTORC1 (PMID:30385734), while post-transcriptionally the protein is downregulated by miR-485-5p targeting the APOA5*2 3′ UTR variant (PMID:24387992) and by PC7 (PCSK7)-mediated lysosomal degradation (PMID:31945259). Loss-of-function mutations—including truncations (Q97X, Q139X, Q148X) and the signal-peptide variant S19W that halves secretion efficiency—cause severe hypertriglyceridemia (type V hyperlipidemia) (PMID:16531747, PMID:15941721), and ApoA5 deficiency additionally promotes hepatic steatosis through destabilization of NR1D1 mRNA independently of plasma TG effects (PMID:38505614).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2005 High

    Establishing how the common S19W variant causes reduced ApoA5 function: the Trp-19 signal peptide impairs ER translocation, reducing secretion ~50%, providing the first molecular explanation for APOA5*3 haplotype-associated hypertriglyceridemia.

    Evidence Molecular modeling of signal peptide insertion angle plus secretion assays of SEAP fusion constructs in HepG2/Huh7 cells

    PMID:15941721

    Open questions at the time
    • Whether S19W affects folding or stability beyond translocation was not tested
    • No in vivo secretion kinetics measured
  2. 2005 High

    Identifying a direct transcriptional mechanism: T3/TRβ activates APOA5 through a DR4 thyroid hormone response element, with USF1/USF2 synergistically co-activating at an adjacent E-box, linking thyroid status to TG metabolism.

    Evidence Promoter luciferase assays defining the DR4 element, hepatocyte T3 treatment, and rat thyroid hormone depletion/repletion in vivo

    PMID:15941710

    Open questions at the time
    • Whether other nuclear receptors use the same DR4 element was not addressed
    • Contribution of USF1/2 cooperation in human liver not confirmed
  3. 2006 Medium

    Human loss-of-function genetics proved that APOA5 is required for normal TG metabolism: patients homozygous for truncation mutations (Q97X, Q139X, Q148X) have undetectable plasma ApoA5 and severe type V hyperlipidemia with reduced LPL activity.

    Evidence APOA5 sequencing, plasma ApoA5 ELISA, postheparin LPL activity in homozygous null patients

    PMID:16531747 PMID:18324930

    Open questions at the time
    • Small number of patients limits genotype-phenotype range
    • Whether residual intracellular ApoA5 has hepatic functions was not examined
  4. 2007 High

    In vivo gain-of-function demonstrated that ApoA5 lowers TG by enhancing VLDL catabolism rather than reducing production, and additionally modulates HDL composition by increasing apoA-I/apoE content and LCAT activity.

    Evidence Adenoviral ApoA5 delivery in APOC3-transgenic mice with lipoprotein fractionation, LCAT activity, and cholesterol efflux assays

    PMID:17438339

    Open questions at the time
    • Relative contribution of enhanced catabolism vs. receptor-mediated clearance not separated
    • HDL remodeling mechanism not molecularly defined
  5. 2007 High

    A precise knock-in model confirmed S19W as a causative functional variant in vivo: single-copy APOA5*3 mice had three-fold lower circulating ApoA5 than APOA5*1 mice, validating the secretion defect.

    Evidence Hprt-targeted single-copy haplotype insertion in mice with plasma ApoA5 ELISA

    PMID:17936576

    Open questions at the time
    • TG phenotype in these mice not reported in this study
    • Human heterozygote secretion kinetics not measured
  6. 2008 High

    Structure-function mapping showed that rare APOA5 missense variants impair LPL activation and that C-terminal domains are essential for binding LDL-family receptors LRP1 and LR8, establishing ApoA5 as a dual-function molecule acting on both lipolysis and receptor-mediated uptake.

    Evidence In vitro LPL activity assays with VLDL substrate and receptor binding assays using recombinant mutant ApoA5 proteins

    PMID:18635818

    Open questions at the time
    • Crystal structure of ApoA5-receptor complex not available
    • Whether LPL activation is direct or via ANGPTL modulation was unresolved at this time
  7. 2013 High

    Systematic dissection of three disease mutations revealed that individual residues distinctly contribute to liposome binding, heparin binding, LPL activation, and receptor interactions (LRP1, sortilin, SorLA), establishing that ApoA5's TG-lowering function is multivalent.

    Evidence Recombinant mutant proteins tested in LPL activation, liposome-binding, heparin-binding, and three receptor-binding assays; 3D homology model

    PMID:23307945

    Open questions at the time
    • No high-resolution experimental structure
    • In vivo validation of individual mutant effects not performed
  8. 2014 High

    Post-transcriptional regulation of APOA5 was defined: the c.*158C variant (rs2266788) in the 3′ UTR creates a miR-485-5p binding site that downregulates APOA5 mRNA, providing a mechanistic basis for the APOA5*2 haplotype's association with hypertriglyceridemia.

    Evidence Allele-specific luciferase reporters in HEK293T and HuH-7 cells with miR-485-5p mimics and inhibitors

    PMID:24387992

    Open questions at the time
    • Whether miR-485-5p levels vary physiologically to modulate ApoA5 is unknown
    • Conflicting report on same SNP and miR-3201 binding not reconciled
  9. 2014 High

    The G185C variant was shown to form aberrant disulfide-linked heterodimers with plasma proteins (fibronectin, kininogen-1), sequestering ApoA5 in the lipoprotein-free fraction and impairing its TG-lowering function—a gain-of-toxic-function mechanism distinct from simple loss of expression.

    Evidence AAV-mediated gene transfer in apoa5−/− mice, non-reducing SDS-PAGE, IP-LC/MS-MS of human homozygote plasma

    PMID:25127531

    Open questions at the time
    • Whether other Cys-introducing variants show similar aberrant dimerization not tested
    • Structural basis of disulfide partner selection unknown
  10. 2014 High

    ApoA5 knockdown paradoxically protected against high-fat-diet insulin resistance by reducing tissue TG and DAG uptake, decreasing PKCε/PKCθ activation and enhancing AKT2 signaling, revealing that ApoA5-driven TRL clearance can promote lipotoxic insulin resistance in peripheral tissues.

    Evidence ASO knockdown in mice with hyperinsulinemic-euglycemic clamps, tissue DAG/TG fractionation, PKC translocation and AKT2 phosphorylation assays

    PMID:25548259

    Open questions at the time
    • Whether this insulin-sensitizing effect of ApoA5 loss occurs in humans is unknown
    • Liver-specific vs. systemic effects not fully deconvoluted
  11. 2018 High

    A nutrient-sensing pathway was connected to APOA5: protein restriction induces APOA5 via CREBH, promoting VLDL-TG hydrolysis, while constitutive mTORC1 activation blocks CREBH and blunts this response, linking mTORC1-CREBH-APOA5 as a metabolic adaptation axis.

    Evidence Dietary protein restriction in wild-type, Crebh KO, and constitutively active mTORC1 mice; ASO knockdown; human randomized trial measuring VLDL-ApoA5

    PMID:30385734

    Open questions at the time
    • Whether amino acid sensing or GCN2 pathway feeds into CREBH activation is not defined
    • Human trial was small and confirmatory
  12. 2020 High

    A new post-translational clearance mechanism was identified: PC7 (PCSK7) binds ApoA5 and routes it to lysosomal degradation non-enzymatically; the PC7-R504H variant's phosphorylation by Fam20C attenuates this degradation, and Pcsk7-knockout mice have elevated plasma ApoA5 and LPL activity.

    Evidence Co-IP in HuH7, lysosomal inhibitor rescue, Fam20C phosphorylation assay, Pcsk7−/− mouse on HFD

    PMID:31945259

    Open questions at the time
    • Whether PC7-mediated degradation is regulated by metabolic signals is unknown
    • Stoichiometry and ER-to-lysosome trafficking route not fully mapped
  13. 2021 High

    The long-debated question of whether ApoA5 directly activates LPL was resolved: ApoA5 has no direct effect on LPL but instead lowers TG by physically associating with the ANGPTL3/8 complex and suppressing its LPL-inhibitory activity, with no effect on ANGPTL3, ANGPTL4, or ANGPTL4/8.

    Evidence IP-MS, biolayer interferometry, and functional LPL enzymatic assays with recombinant proteins

    PMID:33762177

    Open questions at the time
    • Structural basis of the ApoA5–ANGPTL3/8 interaction not determined
    • Whether ApoA5 modulates ANGPTL3/8 secretion or only post-secretory activity is unclear
  14. 2024 High

    A liver-intrinsic role for ApoA5 beyond plasma TG control was established: ApoA5 deficiency destabilizes NR1D1 mRNA in hepatocytes, and NR1D1 overexpression rescues steatosis without correcting hypertriglyceridemia, revealing an ApoA5→NR1D1→NAFLD axis.

    Evidence CRISPR/Cas9 ApoA5 KO hamster, AAV8-NR1D1 rescue, NR1D1 mRNA stability assay in HepG2

    PMID:38505614

    Open questions at the time
    • Mechanism by which ApoA5 stabilizes NR1D1 mRNA is unknown
    • Whether this axis operates in human NAFLD is untested
    • Whether ApoA5 affects other hepatic mRNAs not surveyed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of ApoA5–ANGPTL3/8 interaction, how intracellular ApoA5 stabilizes NR1D1 mRNA, whether the insulin-sensitizing effect of ApoA5 loss translates to humans, and the physiological contexts in which PC7-mediated degradation is regulated.
  • No high-resolution structure of ApoA5 or its complexes
  • Mechanism of NR1D1 mRNA stabilization completely undefined
  • Human relevance of DAG/PKC-mediated insulin sensitization by ApoA5 loss not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0048018 receptor ligand activity 2
Localization
GO:0005576 extracellular region 4 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
ANGPTL3ANGPTL8APOC3LRP1PCSK7SORL1SORT1USF1
Complex memberships
ANGPTL3/8-ApoA5 complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 ApoA5 lowers triglycerides by associating with and suppressing the ANGPTL3/8 complex, thereby relieving ANGPTL3/8-mediated LPL inhibition; ApoA5 has no direct 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 of LPL activity Journal of lipid research High 33762177
2005 The APOA5*3 haplotype-defining S19W (c.56C>G) variant reduces ApoAV secretion by ~50% from hepatic cells; molecular modeling shows Trp-19 increases the angle of insertion of the signal peptide at the lipid/water interface, predicting impaired translocation, confirmed by reduced secretion of a Trp-19-SEAP fusion protein vs. Ser-19-SEAP. Molecular modeling of signal peptide, in vitro secretion assay (HepG2 cells transfected with SEAP fusion constructs), in vitro transcription/translation assays, primer extension inhibition assays, luciferase reporter assays (Huh7 cells) The Journal of biological chemistry High 15941721
2007 ApoA5 delivered to livers of APOC3 transgenic mice reduces plasma TG via enhanced VLDL catabolism (not altered production), reduces apoC-III content in VLDL, and modulates HDL maturation by increasing apoA-I and apoE content and LCAT activity in HDL. Adenovirus-mediated hepatic gene transfer of apoA-V cDNA in APOC3 transgenic mice; plasma lipoprotein fractionation, LCAT activity assay, cholesterol efflux assay Journal of lipid research High 17438339
2008 Several rare APOA5 missense variants (E255G, G271C, H321L, G185C) reduce in vitro LPL activation when using VLDL as substrate; truncation variants (Q139X, Q148X, G271C) abolish binding to LDL-family receptors LR8 and LRP1, indicating that C-terminal lipid-binding domains are required for receptor interaction. Sequencing of APOA5 in hypertriglyceridemic patients; in vitro LPL activity assay with VLDL substrate; receptor binding assays with LR8 and LRP1 Arteriosclerosis, thrombosis, and vascular biology High 18635818
2013 Three APOA5 mutations [p.(Ser232_Leu235)del, p.Leu253Pro, p.Asp332ValfsX4] each impair a distinct combination of LPL activation, liposome binding, heparin binding, and LRP1/sortilin/SorLA receptor binding, as shown by structural modeling and in vitro functional assays; full-length apoA-V 3D model reveals that affected residues are critical structural determinants. Recombinant protein expression/purification, LPL activation assay, liposome-binding assays, heparin-binding assay, LRP1/sortilin/SorLA binding assays, 3D homology modeling Journal of lipid research High 23307945
2014 The hypertriglyceridemia-associated G185C (p.Gly185Cys, rs2075291) variant of apoA-V forms aberrant disulfide-linked heterodimers with plasma proteins including fibronectin and kininogen-1, sequestering >50% of G162C apoA-V in the lipoprotein-free fraction and impairing its lipoprotein-binding and TG-modulating functions. AAV2/8-mediated gene transfer in apoa5(-/-) mice, plasma fractionation, non-reducing SDS-PAGE immunoblot, immunoprecipitation followed by LC/MS-MS of human plasma from variant homozygotes Arteriosclerosis, thrombosis, and vascular biology High 25127531
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; this mechanism explains the hypertriglyceridemic effect of the APOA5*2 haplotype. Luciferase reporter assays in HEK293T and HuH-7 cells co-transfected with APOA5 3' UTR reporter and miR-485-5p precursor; miR-485-5p inhibitor rescue experiment; bioinformatic miRNA binding site prediction American journal of human genetics High 24387992
2014 The APOA5 3' UTR variant rs2266788 C allele destroys a miR-3201 binding site, prolonging APOA5 mRNA half-life and increasing APOA5 expression levels, thereby elevating plasma triglycerides and contributing to coronary artery disease severity. Luciferase reporter assay with 3' UTR constructs, mRNA stability assay, genotyping in case-control cohort Journal of the American College of Cardiology Medium 25034063
2005 Thyroid hormone (T3) directly regulates APOA5 transcription through a functional DR4 thyroid hormone response element in the APOA5 promoter; USF1 and USF2 cooperate with TR at an adjacent E-box to synergistically activate APOA5 in a ligand-dependent manner, increasing apoAV levels and lowering triglycerides in rats. T3/TRβ ligand treatment of hepatocytes (mRNA and protein measurement), APOA5 promoter luciferase reporter assays, DR4 element identification, rat in vivo thyroid hormone depletion/repletion experiments The Journal of biological chemistry High 15941710
2018 Protein restriction (PR) increases VLDL-bound APOA5 expression via the transcription factor CREBH, promoting VLDL-TG hydrolysis and clearance; constitutive mTORC1 activation blocks CREBH activation and blunts APOA5 induction, causing PR-resistant hypertriglyceridemia. PR also reduces VLDL-TG secretion independently of CREBH-APOA5. Mouse dietary protein restriction models, antisense oligonucleotide knockdown, Crebh KO mice, constitutive mTORC1 activation mice, VLDL turnover assays, human randomized controlled trial measuring VLDL APOA5 JCI insight High 30385734
2014 ApoA5 knockdown in mice using antisense oligonucleotides increases plasma TG ~3-fold, decreases TG clearance, and reduces liver and skeletal muscle TG uptake; in high-fat-diet mice, ApoA5 ASO treatment protects against insulin resistance by decreasing diacylglycerol (DAG) content, reducing PKCε and PKCθ activation, and increasing insulin-stimulated AKT2 phosphorylation in liver and muscle. Antisense oligonucleotide knockdown of ApoA5 in mice, hyperinsulinemic-euglycemic clamps, tissue lipid fractionation (DAG/TG measurement), PKC activity assay, AKT2 phosphorylation by Western blot, plasma TG clearance Journal of lipid research High 25548259
2007 Introduction of the APOA5*3-defining S19W allele into mice at a single chromosomal copy (via Hprt-targeted insertion) results in three-fold lower circulating human ApoAV plasma levels compared to the common APOA5*1 or APOA5*2 haplotypes, confirming that S19W is a functional variant that reduces protein secretion/plasma levels. Targeted single-copy haplotype insertion at Hprt locus in mice; plasma human ApoAV measurement by ELISA Genomics High 17936576
2020 PC7 (PCSK7) binds to apoA-V and enhances its lysosomal degradation in a non-enzymatic fashion via an ER-lysosomal pathway; degradation is inhibited by bafilomycin A1, chloroquine, and NH4Cl. The natural PC7 R504H variant promotes Ser505 phosphorylation by Fam20C, and the phosphomimetic PC7-S505E degrades apoA-V less efficiently. In Pcsk7(-/-) mice on HFD, plasma apoA-V and adipocyte LPL activity are increased. Co-expression in HuH7 cells, co-immunoprecipitation, lysosomal inhibitor experiments, Fam20C phosphorylation assay, Pcsk7(-/-) mouse model with plasma apoA-V and LPL activity measurement The FEBS journal High 31945259
2006 ApoAV interacts with apoC-III in a complex manner in hypertriglyceridemic patients; when controlling for apoC-III levels, the positive correlation between apoA-V and TG disappears, while apoC-III remains independently correlated with TG, suggesting apoC-III dominates over apoA-V in setting TG levels in severe HTG. Validated ELISA for plasma apoA-V measurement in HTG patients and controls; partial correlation analysis controlling for apoC-III Journal of lipid research Medium 16861622
2006 Human patients homozygous for APOA5 truncation mutations (Q97X, Q148X, Q139X) have complete apoA-V deficiency in plasma, demonstrating that the C-terminal lipid-binding domain is required for stable circulating protein; these mutations result in severe type V hyperlipidemia with reduced postheparin LPL activity. APOA5 gene sequencing, plasma apoA-V measurement (ELISA/Western blot), postheparin LPL activity assay, apoB-100 kinetic studies, apoA-V lipoprotein association by Western blot Current opinion in lipidology / Journal of internal medicine Medium 16531747 18324930
2024 ApoA5 deficiency in hamsters (CRISPR/Cas9 knockout) causes hypertriglyceridemia and hepatic steatosis; mechanistically, loss of ApoA5 destabilizes NR1D1 mRNA in hepatocytes, reducing NR1D1 protein; AAV8-mediated hepatic NR1D1 overexpression ameliorates fatty liver without correcting plasma TG, identifying a novel ApoA5→NR1D1→NAFLD axis. CRISPR/Cas9 ApoA5 knockout hamster, AAV8 NR1D1 overexpression rescue, in vitro NR1D1 mRNA stability assay in HepG2 cells, plasma lipid and liver histology measurements Theranostics High 38505614
2016 DNA methylation at the CpG island in APOA5 exon 3 positively correlates with circulating TG levels and, in combination with APOA5 SNPs (-1131T>C, S19W, 724C>G), additively determines individual predisposition to hypertriglyceridemia, establishing epigenetic regulation of APOA5 as a mechanism modulating TG levels. Pyrosequencing of APOA5 promoter, exon 2, and exon 3 CpG island methylation in a recruit-by-genotype cohort; correlation analysis with plasma TG Clinical science Low 27613158
2012 Vitamin D-dependent APOA5 promoter polymorphism rs10750097 modulates APOA5 promoter activity in a 25-hydroxyvitamin D-dependent manner, as shown by allele-specific luciferase assays in HEP3B and HEK293 cells, affecting HDL-C levels. Luciferase reporter assays with allele-specific APOA5 promoter constructs in HEP3B and HEK293 cells treated with vitamin D; population genetic analysis Atherosclerosis Medium 22425169

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 530 25487149
2012 Mutations in LPL, APOC2, APOA5, GPIHBP1 and LMF1 in patients with severe hypertriglyceridaemia. Journal of internal medicine 201 22239554
2004 Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study. Journal of lipid research 138 15342688
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
2003 The single nucleotide polymorphism -1131T>C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides in patients with hyperlipidemia. Journal of molecular medicine (Berlin, Germany) 78 12937897
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 70 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 60 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
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
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 51 24387992
2014 ApoA5 knockdown improves whole-body insulin sensitivity in high-fat-fed mice by reducing ectopic lipid content. Journal of lipid research 51 25548259
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
2017 Update on APOA5 Genetics: Toward a Better Understanding of Its Physiological Impact. Current atherosclerosis reports 47 28500476
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 45 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 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
2013 Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia. Journal of lipid research 40 23307945
2018 Dietary protein restriction reduces circulating VLDL triglyceride levels via CREBH-APOA5-dependent and -independent mechanisms. JCI insight 39 30385734
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
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 38 21889769
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
2017 Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia. Scientific reports 30 29263402
2008 Influence of apoA-V gene variants on postprandial triglyceride metabolism: impact of gender. Journal of lipid research 30 18263854
2007 Rare APOA5 mutations--clinical consequences, metabolic and functional effects: an ENID review. Atherosclerosis 29 17222847
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 29 17726453
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
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
2017 Detection of susceptibility loci on APOA5 and COLEC12 associated with metabolic syndrome using a genome-wide association study in a Taiwanese population. Oncotarget 24 29212154
2014 Association of USF1 and APOA5 polymorphisms with familial combined hyperlipidemia in an Italian population. Molecular and cellular probes 24 25308402
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
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
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
2009 Modulation of phenotypic expression of APOA5 Q97X and L242P mutations. Atherosclerosis 20 19447388
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
2017 Admixture mapping in two Mexican samples identifies significant associations of locus ancestry with triglyceride levels in the BUD13/ZNF259/APOA5 region and fine mapping points to rs964184 as the main driver of the association signal. PloS one 17 28245265
2015 Relationship of the APOA5/A4/C3/A1 gene cluster and APOB gene polymorphisms with dyslipidemia. Genetics and molecular research : GMR 16 26345861
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
2024 Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters. Theranostics 14 38505614
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 14 31165758
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
2017 APOA5 Gene Polymorphisms and Cardiovascular Diseases: Metaprediction in Global Populations. Nursing research 13 28252576