{{Rsnum
|rsid=7412
|Gene=APOE
|Chromosome=19
|position=44908822
|Orientation=plus
|ReferenceAllele=C
|MissenseAllele=T
|GMAF=0.07392
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=APOE
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 0.0 | 0.0 | 0.0
| HCB | 82.0 | 18.0 | 0.0
| JPT | 89.4 | 10.6 | 0.0
| YRI | 83.3 | 16.7 | 0.0
| ASW | 78.6 | 19.6 | 1.8
| CHB | 82.0 | 18.0 | 0.0
| CHD | 86.0 | 14.0 | 0.0
| GIH | 92.1 | 6.9 | 1.0
| LWK | 89.6 | 10.4 | 0.0
| MEX | 89.3 | 10.7 | 0.0
| MKK | 87.8 | 12.2 | 0.0
| TSI | 90.9 | 9.1 | 0.0
| HapMapRevision=28
}}The ancestral allele is C. The [[rs7412]](T) allele, also known as Arg176Cys, generally indicates the presence of an Apoε2 allele; see the [[ApoE]] page for a full discussion of the ApoE alleles and their association with [[Alzheimer's disease]].

Another SNP related to ApoE is [[rs429358]].

In a study of 67 mostly Caucasian patients prescribed the atypical antipsychotic [[olanzapine]], carriers of a [[rs7412]](C) allele were more likely to gain significant weight compared to [[rs7412]](T;T) carriers, as assessed by physiogenomic analysis of corresponding weight profiles. Two other SNPs, [[rs5092]] and [[rs4765623]], were also significantly associated with weight profiles in these patients.{{PMID|17199131}}

{{omim
|desc=APOE2 ISOFORMS
|id=107741
|rsnum=7412
|variant=0001
}}
{{omim
| id = 107741
| variant = 0019
| desc    = HYPERLIPOPROTEINEMIA, TYPE III, ASSOCIATED WITH APOE2-FUKUOKA
| rsnum   = 7412
}}
{{ neighbor
| rsid = 769455
| distance = 39
}}
{{ neighbor
| rsid = 28931579
| distance = 414
}}

{{omim
|desc=STROKE, ISCHEMIC
|id=601367
|rsnum=7412
}}

{{PharmGKB
|RSID=rs7412
|Name_s=APOE: Arg158Cys (g.8041C>T, c.526C>T, p.Arg176Cys in dbSNP build 130)
|Gene_s=APOE, APOC1
|Feature=
|Evidence=PubMed ID:199847
|Annotation=Risk or phenotype-associated allele: The ApoE E2 allele is a combination of rs429358 T (130Cys) and rs7412 T (176Cys). Phenotype: The Apo E2 allele contributes to increased risk of type III hyperlipoproteinemia, characterized by increased cholesterol and triglyceride levels, the presence of beta-VLDL (cholesterol-enriched remnants of intestinal chylomicrons and hepatic VLDL), xanthomas, and premature vascular disease, both coronary heart disease and peripheral artery disease. Study size: Three multiplex, multigenerational pedigrees, and case control study of 5 probands versus 94 controls. Study population/ethnicity: Germans. Significance metric(s): N/A. Type of association: CO; GN
|Drugs=
|Drug Classes=
|Diseases=Arteriosclerosis; Hyperlipoproteinemia Type III; Hyperlipoproteinemias; Vascular Diseases
|Curation Level=Curated
|PharmGKB Accession ID=PA165109611
}}

{{PMID Auto
|PMID=20406466
|Title=Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey
|OA=1
}}
{{PMID Auto
|PMID=20429872
|Title=Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and [[hypertriglyceridemia]]: results of the ICARIA genetic sub-study
|OA=1
}}

{{PharmGKB
|RSID=rs7412
|Name_s=APOE: 4075C>T, p.Arg158Cys, (g.8041C>T, c.526C>T, p.Arg176Cys in dbSNP build 130)
|Gene_s=APOE, APOC1
|Feature=
|Evidence=PubMed ID:16433808
|Annotation=Risk or phenotype-associated allele: ApoE E4 allele (rs429358 C, rs7412 C) (130Arg, 176Arg). Phenotype: Increased incidence of chronic plaque psoriasis and guttate psoriasis, but no difference in response of psoriasis to the drug acitretin. Study size: 306 cases, 137 controls. Study population/ethnicity: Patients with chronic plaque psoriasis (n = 212), guttate psoriasis (n = 94). Significance metric(s): p =0.008 Type of association: CO; GN
|Drugs=acitretin
|Drug Classes=
|Diseases=Psoriasis
|Curation Level=Curated
|PharmGKB Accession ID=PA162355842
}}

{{PharmGKB
|RSID=rs7412
|Name_s=APOE: Arg158Cys; 2198C>T; ApoE epsilon 2
|Gene_s=APOE, APOC1
|Feature=
|Evidence=PubMed ID:15809899; PubMed ID:16417409; PubMed ID:17700365
|Annotation=The ApoE epsilon2 variant (2198T) is associated with hyperlipidemia (elevated triglyceride levels) in HIV-infected individuals treated with ritonavir.
|Drugs=ritonavir
|Drug Classes=
|Diseases=HIV; HIV Infections; Hyperlipidemias
|Curation Level=Curated
|PharmGKB Accession ID=PA162360001
}}

{{PharmGKB
|RSID=rs7412
|Name_s=APOE: epsilon3, defined as rs429358 T 130Cys + rs7412 C 176Arg
|Gene_s=APOE, APOC1
|Feature=
|Evidence=PubMed ID:9804125
|Annotation=Risk or phenotype-associated allele: APOE: epsilon3/epsilon3 (defined as rs429358 T/T 130Cys/Cys + rs7412 C/C 176Arg/Arg). Phenotype: Neurodegenerative disease characterized by asymmetric parietal atrophy, visuospatial dysfunction, incomplete Balint&apos;s syndrome, environmental agnosia, left-sided motor symptoms including dystonic postures and myoclonus in the left hand, without significant dementia (as in posterior cortical atrophy) was observed in a woman with early-onset neurodegenerative disease progressing 10 years from onset at age 52 to death. Study size: 1. Study population/ethnicity: Right-handed female/Japanese. Significance metric(s): non significant case report. Type of association: CO; GN
|Drugs=
|Drug Classes=
|Diseases=Neurodegenerative Diseases; Posterior Cortical Atrophy
|Curation Level=Curated
|PharmGKB Accession ID=PA165110265
}}

{{PharmGKB
|RSID=rs7412
|Name_s=APOE: Arg158Cys (g.8041C>T, c.526C>T, p.Arg176Cys in dbSNP build 130)
|Gene_s=APOE, APOC1
|Feature=
|Evidence=PubMed ID:10736278
|Annotation=Risk or phenotype-associated allele: The ApoE E4 allele is a combination of rs429358 C (130Arg) and rs7412 C (176Arg). Phenotype: The Apo E4 allele is associated with 80 percent increased risk of dying (mortality risk ratio = 1.8) compared with other patients upon evaluation at 5.5 years following survival of myocardial infarction. ApoE E4 carriers who had high Lp(a) levels had a risk ratio of 3.7 of coronary death. Simvastatin treatment reduced the mortality risk to 0.33 in Apoe E4 carriers and to 0.66 in other patients (p = 0.23 for treatment by genotype interaction). Study size: 966 survivors of myocardial infarction enrolled in the Scandinavian Simvastatin Survival Study. Study population/ethnicity: Danish and Finnish. Significance metric(s): mortality risk ratio = 1.8. Type of association: CO; PD; GN
|Drugs=simvastatin
|Drug Classes=
|Diseases=Infarction; Myocardial Infarction
|Curation Level=Curated
|PharmGKB Accession ID=PA165109613
}}

{{PharmGKB
|RSID=rs7412
|Name_s=APOE: Arg158Cys (g.8041C>T, c.526C>T, p.Arg176Cys in dbSNP build 130)
|Gene_s=APOE, APOC1
|Feature=
|Evidence=PubMed ID:9343467
|Annotation=Risk or phenotype-associated allele: The APOE E4 allele is a combination of rs429358 C (130Arg) and rs7412 C (176Arg). Phenotype: The APOE E4 allele (130Arg, 176Arg) was studied relative to the E3 (130Cys, 176Arg) and E2 (130Cys, 176Cys) alleles. Relative to the homozygous E3/E3 diplotype, Caucasians showed increased risk of Alzheimer Disease (AD): OR = 2.6 for E4/E2, OR = 3.2 for E4/E3, OR = 14.9 for E4/E4. The E2 allele was protective against risk of AD: OR = 0.6 for E2/E2, OR = 0.6 for E3/E2. Japanese showed greater increased risk of AD than Caucasians: OR=5.6 for E3/E4, OR = 33.1 for E4/E4. Study size: 5930 patients who met criteria for probable or definite AD, and 8607 controls without dementia. Study population/ethnicity: A clinic-/autopsy-based case-control study of patients between 40 and 90 years old recruited from clinical, community, and brain bank sources./Caucasian, African American, Hispanic, Japanese. Significance metric(s): OR. Type of association: CO; GN
|Drugs=
|Drug Classes=
|Diseases=Alzheimer Disease
|Curation Level=Curated
|PharmGKB Accession ID=PA165109615
}}

{{PharmGKB
|RSID=rs7412
|Name_s=APOE: Arg158Cys (g.8041C>T, c.526C>T, p.Arg176Cys in dbSNP build 130)
|Gene_s=APOE, APOC1
|Feature=
|Evidence=PubMed ID:18498549
|Annotation=Risk or phenotype-associated allele: The E3 and E4 alleles of APOE, defined by the combined genotype at rs429358T>C (Cys130Arg) and rs7412C>T (Arg176Cys). Phenotype: The APOE E3 allele (130Cys, 176Arg) and E4 (130Arg, 176Arg) alleles were protective. Carriers of the E3 allele had significantly higher average macular thickness in both eyes (p = 0.012), and significantly better visual acuity (p = 0.041) than non-E3 carriers. E4 carriers showed reduced incidence of cataract than non-APOE4 carriers (p = 0.039). Study size: 32 patients who underwent cataract surgery in both eyes, and 56 controls. Study population/ethnicity: Patients from London, England aged 50-75 years old. Significance metric(s): p-value. Type of association: CO; GN
|Drugs=
|Drug Classes=
|Diseases=Cataract; Macular Degeneration
|Curation Level=Curated
|PharmGKB Accession ID=PA165109617
}}

{{PMID Auto
|PMID=21263195
|Title=An APOE Haplotype Associated with Decreased ?4 Expression Increases the Risk of Late Onset Alzheimer's Disease
}}

{{PMID Auto
|PMID=22174202
|Title=Apolipoprotein E Gene Polymorphisms Are Strong Predictors of Inflammation and Dyslipidemia in Rheumatoid Arthritis
}}

{{PMID Auto
|PMID=19752398
|Title=Gene variants and pravastatin LDL lowering response in prosper
|OA=1
}}

{{PMID Auto GWAS
|PMID=22331829
|Trait=None
|Title=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.
|RiskAllele=
|Pval=2E-47
|OR=6.2000
|ORtxt=None
}}

{{PMID Auto GWAS
|PMID=22286219
|Trait=None
|Title=Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
|RiskAllele=
|Pval=3E-58
|OR=0.7500
|ORtxt=None
|OA=1
}}

{{ClinVar
|rsid=7412
|Reversed=0
|FwdREF=C
|FwdALT=T
|REF=C
|ALT=T
|RSPOS=45412079
|CHROM=19
|GMAF=0.0742
|dbSNPBuildID=52
|SSR=0
|SAO=1
|VP=0x050368000000150517130100
|GENEINFO=APOE:348
|GENE_NAME=APOE
|GENE_ID=348
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000019.9:g.45412079C>T
|CLNORIGIN=1
|CLNSIG=5
|Tags=PM;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPROD;OTHERKG;PH3;LSD;MTP;OM
|CAF=0.9261; 0.07392
|CLNACC=RCV000019427.26; RCV000019428.26; RCV000019439.26; RCV000019452.27; RCV000019454.26
|CLNDBN=APOE2 ISOFORMS; Familial type 3 hyperlipoproteinemia; Apolipoproteinemia E1
|CLNSRC=GTR; OMIM Allelic Variant
|CLNSRCID=GTR000502514; 107741.0001; 107741.0009; 107741.0019; 107741.0021
|COMMON=1
|Disease=APOE2 ISOFORMS; Familial type 3 hyperlipoproteinemia; Apolipoproteinemia E1
|CLNDSDB=MedGen:SNOMED_CT
|CLNDSDBID=C0020479:398796005
}}

{{PMID|15113403|OA=1
}} Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis.

{{PMID|15157284|OA=1
}} Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

{{PMID|16603077|OA=1
}} Variation at APOE and STH loci and Alzheimer's disease.

{{PMID|17048007|OA=1
}} Association of warfarin dose with genes involved in its action and metabolism.

{{PMID|17356695|OA=1
}} Variation in GYS1 interacts with exercise and gender to predict cardiovascular mortality.

{{PMID|17357073|OA=1
}} Genetic analysis of 103 candidate genes for coronary artery disease and associated phenotypes in a founder population reveals a new association between endothelin-1 and high-density lipoprotein cholesterol.

{{PMID|17434289|OA=1
}} Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association.

{{PMID|17456829|OA=1
}} Evaluation of genetic factors for warfarin dose prediction.

{{PMID|17658295}} Association of ApoE genetic variants with obstructive sleep apnea in children.

{{PMID|17672902|OA=1
}} Subarachnoid hemorrhage: tests of association with apolipoprotein E and elastin genes.

{{PMID|17903299|OA=1
}} A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study.

{{PMID|18034366}} Lack of replication of genetic associations with human longevity.

{{PMID|18216863|OA=1
}} Genetic determinants of basal C-reactive protein expression in Filipino systemic lupus erythematosus families.

{{PMID|18254975|OA=1
}} Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat.

{{PMID|18275964|OA=1
}} Low-density lipoprotein and high-density lipoprotein cholesterol levels in relation to genetic polymorphisms and menopausal status: the Atherosclerosis Risk in Communities (ARIC) Study.

{{PMID|18378515|OA=1
}} APOE/C1/C4/C2 hepatic control region polymorphism influences plasma apoE and LDL cholesterol levels.

{{PMID|18513389|OA=1
}} New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

{{PMID|18596683|OA=1
}} Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.

{{PMID|18603647|OA=1
}} Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.

{{PMID|18823527|OA=1
}} A genome-wide association study for late-onset Alzheimer's disease using DNA pooling.

{{PMID|18974842|OA=1
}} Gender differences in genetic risk profiles for cardiovascular disease.

{{PMID|18976728|OA=1
}} Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE.

{{PMID|19001172|OA=1
}} Analyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci.

{{PMID|19014573|OA=1
}} Application of two machine learning algorithms to genetic association studies in the presence of covariates.

{{PMID|19058936|OA=1
}} A polymorphism of apolipoprotein E (APOE) gene is associated with age at natural menopause in Caucasian females.

{{PMID|19118814|OA=1
}} Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease.

{{PMID|19131662|OA=1
}} A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.

{{PMID|19262956}} GAB2 gene does not modify the risk of Alzheimer's disease in Spanish APOE 4 carriers.

{{PMID|19263529|OA=1
}} Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.

{{PMID|19285141|OA=1
}} Genetic determinants of target and novelty-related event-related potentials in the auditory oddball response.

{{PMID|19299407|OA=1
}} Replication of genetic associations with plasma lipoprotein traits in a multiethnic sample.

{{PMID|19336475|OA=1
}} Integrated associations of genotypes with multiple blood biomarkers linked to coronary heart disease risk.

{{PMID|19377787}} Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals.

{{PMID|19541455}} Apolipoprotein-E gene variants associated with cardiovascular risk factors in antipsychotic recipients.

{{PMID|19667110}} Identification of genetic variants associated with response to statin therapy.

{{PMID|19668339|OA=1
}} Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease.

{{PMID|19756043|OA=1
}} A simple and efficient algorithm for genome-wide homozygosity analysis in disease.

{{PMID|19787382|OA=1
}} Introduction to the DISRUPT postprandial database: subjects, studies and methodologies.

{{PMID|19802338|OA=1
}} Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication.

{{PMID|19913121|OA=1
}} Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.

{{PMID|19936222|OA=1
}} Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis.

{{PMID|19951432|OA=1
}} Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease.

{{PMID|20031563}} Genetic variants associated with myocardial infarction risk factors in over 8000 individuals from five ethnic groups: The INTERHEART Genetics Study.

{{PMID|20031582}} Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort.

{{PMID|20082485|OA=1
}} Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women.

{{PMID|20451875|OA=1
}} Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans.

{{PMID|20565774|OA=1
}} Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

{{PMID|20663622}} A susceptible haplotype within APOE gene influences BMD and intensifies the osteoporosis risk in postmenopausal women of Northwest India.

{{PMID|20682755|OA=1
}} A pilot study of gene/gene and gene/environment interactions in Alzheimer disease.

{{PMID|20832063}} Exploring genetic determinants of plasma total cholesterol levels and their predictive value in a longitudinal study.

{{PMID|21215387|OA=1
}} IQ, educational attainment, memory and plasma lipids: associations with apolipoprotein E genotype in 5995 children.

{{PMID|21228733|OA=1
}} Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients.

{{PMID|21285406}} Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study.

{{PMID|21379329|OA=1
}} Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE.

{{PMID|21647738|OA=1
}} Genome-wide association with C-reactive protein levels in CLHNS: evidence for the CRP and HNF1A loci and their interaction with exposure to a pathogenic environment.

{{PMID|21689001}} Association study between apolipoprotein E gene polymorphism and diabetic nephropathy in a Taiwanese population.

{{PMID|21703254}} APOE haplotypes are associated with human longevity in a Central Italy population: evidence for epistasis with HP 1/2 polymorphism.

{{GET Evidence
|gene=APOE
|aa_change=Arg176Cys
|aa_change_short=R176C
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=other
|quality_scores=Array
|dbsnp_id=rs7412
|overall_frequency_n=547
|overall_frequency_d=8056
|overall_frequency=0.0678997
|n_genomes=8
|n_genomes_annotated=0
|n_haplomes=8
|n_articles=7
|n_articles_annotated=6
|gene_in_genetests=Y
|in_pharmgkb=Y
|pph2_score=1.0
|genetests_testable=Y
|nblosum100=8
|autoscore=4
|webscore=N
|n_web_uneval=10
|summary_short=This is generally known as the ApoE2 variant of ApoE and is associated with a decreased risk of Alzheimer's disease.
}}

{{PMID Auto GWAS
  |PMID=23067351
  |Trait=LDL cholesterol
  |Title=High density GWAS for LDL cholesterol in African Americans using electronic medical records reveals a strong protective variant in APOE.
  |RiskAllele=
  |Pval=2E-9
  |OR=12.30
  |ORtxt=[8.4-16.3] mg/dL decrease
  |OA=1
}}

{{PMID Auto
|PMID=23050023
|Title=Association of genetic variants influencing lipid levels with coronary artery disease in Japanese individuals
|OA=1
}}

{{PMID Auto
|PMID=24291031
|Title=Association of APOE, GCPII and MMP9 polymorphisms with common diseases and lipid levels in an older adult/elderly cohort
}}

{{PMID Auto
|PMID=22651940
|Title=The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case-control cohorts.
}}

{{PMID Auto
|PMID=22710912
|Title=TOMM40, APOE, and APOC1 in primary progressive aphasia and frontotemporal dementia.
}}

{{PMID Auto
|PMID=22715478
|Title=Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
}}

{{PMID Auto
|PMID=22898894
|Title=Pleiotropy and allelic heterogeneity in the TOMM40-APOE genomic region related to clinical and metabolic features of hepatitis C infection.
}}

{{PMID Auto
|PMID=22922093
|Title=Low-density lipoprotein cholesterol and risk of gallstone disease: a Mendelian randomization study and meta-analyses.
}}

{{PMID Auto
|PMID=23100282
|Title=Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.
|OA=1
}}

{{PMID Auto
|PMID=23430611
|Title=Identification of a functional apolipoprotein E promoter polymorphism regulating plasma apolipoprotein E concentration.
}}

{{PMID Auto
|PMID=23533563
|Title=Novel risk factors for premature peripheral arterial occlusive disease in non-diabetic patients: a case-control study.
|OA=1
}}

{{PMID Auto
|PMID=25085564
|Title=Influence of multiple
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}