Gene: APOE

Alternate names for this Gene: AD2|APO-E|ApoE4|LDLCQ5|LPG

Gene Summary: The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants.

Gene is located in Chromosome: 19

Location in Chromosome : 19q13.32

Description of this Gene: apolipoprotein E

Type of Gene: protein-coding

rs7412 in APOE gene and Acute Coronary Syndrome PMID 28753643 2017 Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.

rs429358 in APOE gene and Age related macular degeneration PMID 26691988 2016 A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

rs429358 in APOE gene and Alzheimer Disease, Early Onset PMID 10799751 2000 Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease.

PMID 22381401 2012 Association between apolipoprotein E gene polymorphism and the risk of vascular dementia: a meta-analysis.

PMID 23060451 2012 APOE4-specific changes in Aβ accumulation in a new transgenic mouse model of Alzheimer disease.

PMID 9343467 1997 Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.

PMID 19605830 2009 Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect.

PMID 23296339 2013 Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy.

PMID 23571587 2013 Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.

PMID 27260402 2016 Differential burden of rare protein truncating variants in Alzheimer's disease patients compared to centenarians.

rs1081105 in APOE gene and Alzheimer's Disease PMID 29777097 2018 GWAS on family history of Alzheimer's disease.

PMID 30617256 2019 Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.

PMID 19136949 2009 Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease.

PMID 22832961 2012 Genome-wide association study of Alzheimer's disease.

PMID 24755620 2014 Overrepresentation of glutamate signaling in Alzheimer's disease: network-based pathway enrichment using meta-analysis of genome-wide association studies.

PMID 19734903 2009 Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.

PMID 30636644 2019 Genome-wide analysis of genetic predisposition to Alzheimer's disease and related sex disparities.

PMID 22005930 2012 Genome-wide association study of Alzheimer's disease with psychotic symptoms.

PMID 21379329 2011 Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE.

PMID 21460841 2011 Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.

PMID 20885792 2010 Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities.

PMID 25027320 2014 SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.

PMID 21123754 2011 Genome-wide association study of CSF biomarkers Abeta1-42, t-tau, and p-tau181p in the ADNI cohort.

PMID 31473137 2019 Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.

PMID 31055733 2019 Genetic heterogeneity of Alzheimer's disease in subjects with and without hypertension.

PMID 23419831 2014 APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study.

PMID 23565137 2013 SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.

PMID 23562540 2013 GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.

rs429358 in APOE gene and Apolipoproteins E measurement (procedure) PMID 28240269 2017 Connecting genetic risk to disease end points through the human blood plasma proteome.

rs405509 in APOE gene and Autoantibody measurement PMID 19734900 2009 Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia.

rs429358 in APOE gene and Blood Protein Measurement PMID 29875488 2018 Genomic atlas of the human plasma proteome.

PMID 30111768 2018 Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease.

PMID 30072576 2018 Co-regulatory networks of human serum proteins link genetics to disease.

rs405509 in APOE gene and C-reactive protein measurement PMID 23505291 2013 Gene-centric analysis identifies variants associated with interleukin-6 levels and shared pathways with other inflammation markers.

PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

PMID 30388399 2018 Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.

PMID 18439548 2008 Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

rs7412 in APOE gene and Cardiovascular Diseases PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs429358 in APOE gene and Cerebral Amyloid Angiopathy PMID 29458411 2018 Genome-wide pleiotropy analysis of neuropathological traits related to Alzheimer's disease.

rs7412 in APOE gene and Coronary Artery Disease PMID 28714975 2017 Association analyses based on false discovery rate implicate new loci for coronary artery disease.

PMID 30104761 2018 Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

PMID 29212778 2018 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.

rs7412 in APOE gene and Coronary heart disease PMID 28753643 2017 Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.

rs429358 in APOE gene and Dementia, Vascular PMID 31473137 2019 Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.

rs440446 in APOE gene and Eosinophil count procedure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs429358 in APOE gene and Exudative age-related macular degeneration PMID 26691988 2016 A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

rs7412 in APOE gene and Finding of Mean Corpuscular Hemoglobin PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs429358 in APOE gene and Geographic Atrophy PMID 26691988 2016 A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

rs429358 in APOE gene and High density lipoprotein measurement PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 25961943 2015 The impact of low-frequency and rare variants on lipid levels.

PMID 31675503 2019 Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 28270201 2017 Exploration of haplotype research consortium imputation for genome-wide association studies in 20,032 Generation Scotland participants.

rs121918393 in APOE gene and Hyperlipoproteinemia Type III PMID 1674745 1991 Apolipoprotein E-4Philadelphia (Glu13----Lys,Arg145----Cys). Homozygosity for two rare point mutations in the apolipoprotein E gene combined with severe type III hyperlipoproteinemia.

PMID 2101409 1991 Identification and characterization of a new variant of apolipoprotein E (apo E-Kochi).

PMID 8287539 1994 Common and rare genotypes of human apolipoprotein E determined by specific restriction profiles of polymerase chain reaction-amplified DNA.

PMID 1361196 1992 Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a premature stop codon in the apolipoprotein E gene.

PMID 7635945 1995 Dominant expression of type III hyperlipoproteinemia. Pathophysiological insights derived from the structural and kinetic characteristics of ApoE-1 (Lys146-->Glu).

PMID 2556398 1989 Apolipoprotein E3-Leiden contains a seven-amino acid insertion that is a tandem repeat of residues 121-127.

PMID 22481068 2012 APOE R136S and p.Leu149del induce autosomal dominant FD and a phenotype indistinguishable from FCHL, respectively.

PMID 2738044 1989 Identification of human apolipoprotein E variant gene: apolipoprotein E7 (Glu244,245----Lys244,245).

PMID 7635945 1995 We have identified a kindred in which heterozygosity for an apoE mutant, apoE-1 (Lys146-->Glu), is dominantly associated with the expression of type III hyperlipoproteinemia.

PMID 22481068 2012 Apolipoprotein E gene mutations in subjects with mixed hyperlipidemia and a clinical diagnosis of familial combined hyperlipidemia.

PMID 22962670 2012 Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline.

PMID 1674745 1991 Apolipoprotein E-4Philadelphia (Glu13----Lys,Arg145----Cys). Homozygosity for two rare point mutations in the apolipoprotein E gene combined with severe type III hyperlipoproteinemia.

PMID 1674745 1991 Apolipoprotein E-4Philadelphia (Glu13----Lys,Arg145----Cys). Homozygosity for two rare point mutations in the apolipoprotein E gene combined with severe type III hyperlipoproteinemia.

rs769452 in APOE gene and Hyperlipoproteinemia Type IIa PMID 26802169 2016 Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France.

PMID 24267230 2013 APOE p.Leu167del mutation in familial hypercholesterolemia.

PMID 22949395 2013 Description of a large family with autosomal dominant hypercholesterolemia associated with the APOE p.Leu167del mutation.

rs429358 in APOE gene and Hyperopia PMID 30098192 2018 Genome-Wide Association Study Identifies a Susceptibility Locus for Comitant Esotropia and Suggests a Parent-of-Origin Effect.

rs429358 in APOE gene and Hypertensive disease PMID 31055733 2019 Genetic heterogeneity of Alzheimer's disease in subjects with and without hypertension.

rs121918397 in APOE gene and LIPOPROTEIN GLOMERULOPATHY PMID 9176854 1997 Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with lipoprotein glomerulopathy.

PMID 10432380 1999 Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three patients with LPG.

PMID 10903326 2000 Recent studies identified several apoE mutations in patients with LPG, including apoE2(R145P) Sendai (apoE-Sendai).

PMID 18077821 2007 APOE Kyoto mutation in European Americans with lipoprotein glomerulopathy.

PMID 10903326 2000 Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops lipoprotein glomerulopathy in ApoE-deficient mice.

PMID 9176854 1997 Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with lipoprotein glomerulopathy.

PMID 10432380 1999 Apo E2 (Arg25Cys) Kyoto is a novel mutation of apo E that is etiologically related to LPG.

rs429358 in APOE gene and Lewy Body Disease PMID 31065058 2019 GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study.

PMID 25188341 2014 Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias.

PMID 29263008 2018 Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study.

rs7412 in APOE gene and Lipids measurement PMID 22286219 2012 Genome-wide association study identifies multiple loci influencing human serum metabolite levels.

rs7412 in APOE gene and Lipoprotein (a) measurement PMID 28512139 2017 A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.

rs429358 in APOE gene and Longevity PMID 31413261 2019 A meta-analysis of genome-wide association studies identifies multiple longevity genes.

rs405509 in APOE gene and Low density lipoprotein cholesterol measurement PMID 23100282 2013 Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.

PMID 22629316 2012 Multi-ethnic analysis of lipid-associated loci: the NHLBI CARe project.

PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

PMID 23067351 2012 SNP rs7412 in APOE was strongly associated with LDL-C in both datasets (p < 5 × 10(-8) ).

PMID 24023260 2013 Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 31551469 2019 Genetic architecture of human plasma lipidome and its link to cardiovascular disease.

PMID 28548082 2017 Whole genome sequencing and imputation in isolated populations identify genetic associations with medically-relevant complex traits.

PMID 31675503 2019 Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

PMID 28334899 2017 Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

PMID 30576415 2019 Very low-depth whole-genome sequencing in complex trait association studies.

PMID 20838585 2010 Longitudinal genome-wide association of cardiovascular disease risk factors in the Bogalusa heart study.

PMID 24507774 2014 Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.

rs429358 in APOE gene and Memory performance PMID 29274321 2018 Genome-wide association study of Alzheimer's disease endophenotypes at prediagnosis stages.

PMID 28800603 2017 Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort.

rs429358 in APOE gene and Mental deterioration PMID 28078323 2017 Genetic architecture of age-related cognitive decline in African Americans.

PMID 24468470 2014 We found 2 independent associations among European-Americans in the 19q13.32 region: rs769449 (APOE intron; p = 3.1 × 10(-20)) and rs115881343 (TOMM40 intron; p = 6.6 × 10(-11)). rs769449 was also associated with cognitive decline among African-Americans (p = 0.005), but rs115881343 was not.

rs429358 in APOE gene and Parkinson Disease PMID 30957308 2019 Parkinson's disease age at onset genome-wide association study: Defining heritability, genetic loci, and α-synuclein mechanisms.

rs429358 in APOE gene and Physical Activity Measurement PMID 29899525 2018 Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE.

rs429358 in APOE gene and Platelet Count measurement PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs429358 in APOE gene and RDW - Red blood cell distribution width result PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7412 in APOE gene and Red Blood Cell Count measurement PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs429358 in APOE gene and Red cell distribution width determination PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7412 in APOE gene and Reticulocyte count (procedure) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs405509 in APOE gene and Serum LDL cholesterol measurement PMID 22629316 2012 Multi-ethnic analysis of lipid-associated loci: the NHLBI CARe project.

PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 23100282 2013 Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.

PMID 23067351 2012 High density GWAS for LDL cholesterol in African Americans using electronic medical records reveals a strong protective variant in APOE.

rs769446 in APOE gene and Serum albumin measurement PMID 22286219 2012 Genome-wide association study identifies multiple loci influencing human serum metabolite levels.

rs405509 in APOE gene and Serum total cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

PMID 28270201 2017 Exploration of haplotype research consortium imputation for genome-wide association studies in 20,032 Generation Scotland participants.

PMID 24023260 2013 Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels.

PMID 31675503 2019 Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

PMID 28548082 2017 Whole genome sequencing and imputation in isolated populations identify genetic associations with medically-relevant complex traits.

PMID 28334899 2017 Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

PMID 25961943 2015 The impact of low-frequency and rare variants on lipid levels.

PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

rs405509 in APOE gene and Squamous cell carcinoma PMID 23103227 2012 Genetic variants at 6p21.1 and 7p15.3 are associated with risk of multiple cancers in Han Chinese.

rs7412 in APOE gene and Systolic Pressure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 30578418 2019 Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.

rs115299243 in APOE gene and Triglycerides measurement PMID 31217584 2019 Genetic analyses of diverse populations improves discovery for complex traits.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 19060911 2009 Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.

PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

PMID 24507774 2014 Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.

rs769449 in APOE gene and Vitiligo PMID 22561518 2012 Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.

rs429358 in APOE gene and Waist-Hip Ratio PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 30239722 2019 Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.

rs429358 in APOE gene and exudative macular degeneration PMID 26691988 2016 A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

rs7412 in APOE gene and response to statin PMID 22331829 2012 Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial.