{{Rsnum
|rsid=4420638
|Gene=APOC1
|Chromosome=19
|position=44919689
|Orientation=plus
|GMAF=0.1635
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=APOC1
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 63.3 | 36.7 | 0.0
| HCB | 74.5 | 25.5 | 0.0
| JPT | 85.7 | 14.3 | 0.0
| YRI | 75.5 | 24.5 | 0.0
| ASW | 52.7 | 47.3 | 0.0
| CHB | 74.5 | 25.5 | 0.0
| CHD | 81.3 | 18.7 | 0.0
| GIH | 87.0 | 13.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 82.8 | 17.2 | 0.0
| MKK | 65.3 | 34.7 | 0.0
| TSI | 74.0 | 26.0 | 0.0
| HapMapRevision=28
}}

Apolipoprotein E [[ApoE]] status is technically defined by two different SNPs, [[rs429358]] and [[rs7412]].  This SNP, [[rs4420638]], is situated about 14kb away in the adjacent ApoC1 gene and is co-inherited with ApoE and thus associated with late-onset [[Alzheimer's disease]].{{PMID|17192785}}

[[rs4420638]] (the proxy SNP) is not independent of [[rs429358]]. These two SNPs are correlated with each other and it's believed that most of the association with AD at rs4420638 is due to its proximity to rs429358. That said, rs4420638 is not a perfect proxy for rs429358 either -- rs4420638 correlates better for certain genotypes and for certain ethnicities. For example, if you have the genotype at rs4420638 that is more correlated with the e4 allele of APOE, you still only have a 50% chance of actually having the e4 allele. And rs4420638 is not very predictive for any genotype in African populations. 

The (G;G) form of this SNP indicates increased risk of [[Alzheimer's disease]], however the probability and amount of increased risk is subject to some disagreement. The initial report concerning this SNP indicated a high likelihood that [[rs4420638]](G;G) homozygotes were predictably ApoE4/ApoE4 homozygotes and thus at significantly (15 fold or higher) risk for Alzheimer's. However, one testing service has estimated [pers. communication] that 25% to 50% of people with the (G;G) are *not* actually ApoE4 homozygotes, and are more likely to be at ~2-3x increased risk based on being ApoE3/ApoE4 heterozygotes. 

If you were tested on [[deCODEme]] or [[23andMe]] v3 platform, ignore this proxy and just check your status at [[rs429358]] and [[rs7412]]. [[23andme]] added [[rs429358]] for people who tested on the v3 platform on 04/14/2011, so you should re-download your data if you haven't.

This [http://www.alzforum.org/new/detail.asp?id=1567 AlzForum.org] article suggests that ApoE4/ApoE4 homozygotes have a ~15-fold increased risk for developing the disease compared to ApoE3/ApoE3 carriers, whereas [[rs4420638]](A;G) individuals have a ~3-fold increased risk.

[[ApoE4]] status is notable as being the variation that several well known scientists, including Nobel Prize winner [[User:Watson|James Watson]], request not to learn when having their own genomes analyzed.

Meta-analyses have also supported the association between the [[ApoE4]] allele and somewhat increased risk for [[heart disease]], with an odds ratio of 1.42 (CI: 1.26 - 1.61).{{PMID| 15488874}}

[http://blog.23andme.com/2009/06/30/genetic-study-casts-doubt-on-inflammatory-marker-as-cause-of-heart-disease/ 23andMe blog] each rs4420638(G) lowered CRP by 21.8% also associated with higher total cholesterol, LDL choelsterol and triglycerides, and lower HDL cholesterol

Note: the [[:Category:On_chip_Affy500k|Affymetrix 500K chip]] is said to poorly tag (ie assay) this particular SNP. {{PMID|17554300|OA=1
}}

According to [https://www.23andme.com/you/community/thread/1144/ a 23andMe discussion] This is one of the SNPs which were re-analyzed April 2009. Customers with older data may wish to redownload. SNPs effected [[rs4420638]], [[rs34276300]], [[rs3091244]], [[rs34601266]], [[rs2033003]], [[rs7900194]], [[rs9332239]], [[rs28371685]], [[rs1229984]], and [[rs28399504]].

G allele is associated with 6.61mg/dl increase in [[LDL cholesterol]] (bad cholesterol). {{PMID|18193043}}

{{PMID Auto GWAS
|PMID=19060906
|Trait=LDL cholesterol
|Title=Common variants at 30 loci contribute to polygenic dyslipidemia
|RiskAllele=G
|Pval=4E-27
|OR=0.29
|ORtxt=[0.17-0.41] SD increase
|OA=1
}}
{{PMID Auto GWAS
|PMID=18802019
|Trait=LDL cholesterol
|Title=Common SNPs in HMGCR in Micronesians and Whites Associated With LDL-Cholesterol Levels Affect Alternative Splicing of Exon13
|RiskAllele=
|Pval=2E-7
|OR=NR
|ORtxt=NR
|OA=1
}}
{{PMID Auto GWAS
|PMID=18262040
|Trait=LDL cholesterol
|Title=LDL-cholesterol concentrations: a genome-wide association study
|RiskAllele=G
|Pval=9.9999999999999995E-21
|OR=0.06
|ORtxt=[0.04-0.08] mmol/L increase
|OA=1
}}
{{PMID Auto GWAS
|PMID=18193044
|Trait=LDL cholesterol
|Title=Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans
|RiskAllele=G
|Pval=9.9999999999999997E-61
|OR=0.19
|ORtxt=[0.15-0.23] % SD higher
|OA=1
}}
{{PMID Auto GWAS
|PMID=18193043
|Trait=LDL cholesterol
|Title=Newly identified loci that influence lipid concentrations and risk of coronary artery disease
|RiskAllele=G
|Pval=3E-43
|OR=6.61
|ORtxt=[NR] mg/dl higher
}}
{{PMID Auto GWAS
|PMID=17998437
|Trait=Alzheimer's disease
|Title=Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease
|RiskAllele=
|Pval=1.9999999999999999E-44
|OR=NR
|ORtxt=NR
}}
{{PMID Auto GWAS
|PMID=17975299
|Trait=Alzheimer's disease
|Title=Sorl1 as an Alzheimer's disease predisposition gene?
|RiskAllele=
|Pval=9.9999999999999993E-40
|OR=NR
|ORtxt=NR
}}
{{PMID Auto GWAS
|PMID=17463246
|Trait=Triglycerides
|Title=Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
|RiskAllele=G
|Pval=2.9999999999999998E-13
|OR=2.40
|ORtxt=% [NR] of variance explained
}}
{{PMID Auto GWAS
|PMID=17474819
|Trait=Late onset Alzheimer's disease
|Title=A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease
|RiskAllele=
|Pval=9.9999999999999993E-40
|OR=4.01
|ORtxt=[NR]
}}

{{PMID Auto
|PMID=19567438
|Title=Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease
|OA=1
}}

{{omim
|desc=APOLIPOPROTEIN E; APOE
|id=107741
|rsnum=4420638
}}
{{PMID Auto
|PMID=19818961
|Title=Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm
|OA=1
}}
{{PMID Auto GWAS
|PMID=19197348
|Trait=Quantitative traits
|Title=Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae
|RiskAllele=G
|Pval=3E-7
|OR=0.28
|ORtxt=[NR] mg/dL increase
|OA=1
}}

{{PharmGKB
|RSID=rs4420638
|Name_s=
|Gene_s=APOC1
|Feature=
|Evidence=PubMed ID:17975299; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Sorl1 as an Alzheimer's disease predisposition gene?. (Initial Sample Size: 664 cases, 422 controls; Replication Sample Size: NR); (Region: 19q13.32; Reported Gene(s): APOE; Risk Allele: rs4420638-?); (p-value= 9.99999999999999E-40).This variant is associated with Alzheimer's disease.
|Drugs=
|Drug Classes=
|Diseases=Alzheimer Disease
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740863
}}

{{PMID Auto
|PMID=19773416
|Title=A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women
|OA=1
}}
{{PMID Auto GWAS
|PMID=20442857
|Trait=Lipoprotein-associated phospholipase A2 activity and mass
|Title=Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study
|RiskAllele=G
|Pval=6E-24
|OR=8.00
|ORtxt=[NR] nmol/ml/min increase
|OA=1
}}
{{PMID Auto GWAS
|PMID=20864672
|Trait=None
|Title=Genetic Variants Influencing Circulating Lipid Levels and Risk of Coronary Artery Disease
|RiskAllele=G
|Pval=2E-40
|OR=0.06
|ORtxt=[0.05-0.07] unit increase
|OA=1
}}

{{PharmGKB
|RSID=rs4420638
|Name_s=
|Gene_s=APOC1
|Feature=
|Evidence=PubMed ID:18976728
|Annotation=In a GWAS of Alzheimer Disease families of self-reported European ancestry, this SNP was found to be associated with Alzheimer Disease.
|Drugs=
|Drug Classes=
|Diseases=Alzheimer Disease
|Curation Level=Curated
|PharmGKB Accession ID=PA162356247
}}

{{PharmGKB
|RSID=rs4420638
|Name_s=
|Gene_s=APOC1
|Feature=
|Evidence=PubMed ID:19060906; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Common variants at 30 loci contribute to polygenic dyslipidemia. (Initial Sample Size: 19,840 individuals; Replication Sample Size: Up to 20,623 individuals); (Region: 19q13.32; Reported Gene(s): APOE, APOC1, APOC4, APOC2; Risk Allele: rs4420638-G); (p-value= 4E-27).This variant is associated with LDL cholesterol.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740256
}}

{{PharmGKB
|RSID=rs4420638
|Name_s=
|Gene_s=APOC1
|Feature=
|Evidence=PubMed ID:18802019; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Common SNPs in HMGCR in Micronesians and Whites Associated With LDL-Cholesterol Levels Affect Alternative Splicing of Exon13. (Initial Sample Size: 2,346 Micronesian individuals; Replication Sample Size: 1,464 European white cases, 1,467 European white controls); (Region: 19q13.32; Reported Gene(s): APOE, APOC1, APOC4, APOC2; Risk Allele: rs4420638-?); (p-value= 0.0000002).This variant is associated with LDL cholesterol.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740853
}}

{{PharmGKB
|RSID=rs4420638
|Name_s=
|Gene_s=APOC1
|Feature=
|Evidence=PubMed ID:17474819; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease. (Initial Sample Size: 664 cases, 422 controls; Replication Sample Size: NR); (Region: 19q13.32; Reported Gene(s): APOE); (p-value= 9.99999999999999E-40).This variant is associated with Late onset Alzheimer's disease.
|Drugs=
|Drug Classes=
|Diseases=Alzheimer Disease
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740866
}}

{{PharmGKB
|RSID=rs4420638
|Name_s=
|Gene_s=APOC1
|Feature=
|Evidence=PubMed ID:17998437; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. (Initial Sample Size: 753 cases, 736 controls; Replication Sample Size: 418 cases, 249 controls); (Region: 19q13.32; Reported Gene(s): APOE, APOC; Risk Allele: rs4420638-?); (p-value= 1.99999999999999E-44).This variant is associated with Alzheimer's disease.
|Drugs=
|Drug Classes=
|Diseases=Alzheimer Disease
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740862
}}

{{PMID Auto GWAS
|PMID=21196492
|Trait=None
|Title=Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus
|RiskAllele=A
|Pval=3E-7
|OR=0.1360
|ORtxt=[0.09-0.19] unit increase
}}

{{PMID Auto GWAS
|PMID=21300955
|Trait=None
|Title=Meta-Analysis of Genome-Wide Association Studies in >80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels
|RiskAllele=A
|Pval=0
|OR=0.2360
|ORtxt=[0.22-0.26] unit increase
|OA=1
}}

{{PMID Auto
|PMID=21149302
|Title=Effects of genetic variants on lipid parameters and dyslipidemia in a Chinese population
|OA=1
}}

{{PMID Auto GWAS
|PMID=21740922
|Trait=None
|Title=A genome-wide association study confirms APOE as the major gene influencing survival in long-lived individuals.
|RiskAllele=
|Pval=2E-16
|OR=None
|ORtxt=None
}}

{{PMID Auto GWAS
|PMID=22054870
|Trait=None
|Title=A genome-wide scan for common variants affecting the rate of age-related cognitive decline.
|RiskAllele=
|Pval=4E-27
|OR=None
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=22005931
|Trait=None
|Title=Genome-wide association analysis of age-at-onset in Alzheimer's disease.
|RiskAllele=
|Pval=1E-12
|OR=None
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=22003152
|Trait=None
|Title=Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies.
|RiskAllele=A
|Pval=5E-30
|OR=0.0540
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=20686565
|Trait=None
|Title=Biological, clinical and population relevance of 95 loci for blood lipids.
|RiskAllele=G
|Pval=4E-21
|OR=1.0600
|ORtxt=None
|OA=1
}}

{{PMID Auto
|PMID=18161859
|Title=Does APOE explain the linkage of Alzheimer's disease to chromosome 19q13?
|OA=1
}}

{{PMID Auto
|PMID=18179892
|Title=Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia.
|OA=1
}}

{{PMID Auto
|PMID=18852197
|Title=Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.
|OA=1
}}

{{PMID Auto
|PMID=19060910
|Title=Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.
|OA=1
}}

{{PMID Auto
|PMID=19161620
|Title=An open access database of genome-wide association results.
|OA=1
}}

{{PMID Auto
|PMID=19204163
|Title=GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association results.
|OA=1
}}

{{PMID Auto
|PMID=19265542
|Title=Performance of random forest when SNPs are in linkage disequilibrium.
|OA=1
}}

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

{{PMID Auto
|PMID=19336575
|Title=Genetic analysis of coronary artery disease single-nucleotide polymorphisms in diabetic nephropathy.
}}

{{PMID Auto
|PMID=19389868
|Title=The coronary artery disease SNP, rs4420638, is associated with diabetic nephropathy rather than end-stage renal disease.
}}

{{PMID Auto
|PMID=19474294
|Title=Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
|OA=1
}}

{{PMID Auto
|PMID=19557197
|Title=NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.
|OA=1
}}

{{PMID Auto
|PMID=19569043
|Title=Genome-wide association studies and the genetic dissection of complex traits.
|OA=1
}}

{{PMID Auto
|PMID=19750184
|Title=Genome-wide association studies for atherosclerotic vascular disease and its risk factors.
|OA=1
}}

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

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

{{PMID Auto
|PMID=20018036
|Title=Using a latent growth curve model for an integrative assessment of the effects of genetic and environmental factors on multiple phenotypes.
|OA=1
}}

{{PMID Auto
|PMID=20339536
|Title=Genome-wide association of lipid-lowering response to statins in combined study populations.
|OA=1
}}

{{PMID Auto
|PMID=20679960
|Title=Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients.
}}

{{PMID Auto
|PMID=20972250
|Title=Genetic loci associated with lipid concentrations and cardiovascular risk factors in the Korean population.
}}

{{PMID Auto
|PMID=22368281
|Title=Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a).
|OA=1
}}

{{PMID Auto GWAS
|PMID=22832961
|Trait=None
|Title=Genome-wide association study of Alzheimer's disease.
|RiskAllele=
|Pval=0
|OR=3.4500
|ORtxt=None
|OA=1
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs4420638
|n_genomes=16
|n_genomes_annotated=0
|n_haplomes=18
|n_articles=2
|n_articles_annotated=2
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=23098650
|Title=Impact of variants within seven candidate genes on statin treatment efficacy
}}

{{PMID Auto
|PMID=23119086
|Title=Variants Identified in a GWAS Meta-Analysis for Blood Lipids Are Associated with the Lipid Response to Fenofibrate
|OA=1
}}

{{PMID Auto
|PMID=23588940
|Title=Association of Polymorphisms Modulating Low-density Lipoprotein Cholesterol with Susceptibility, Severity, and Progression of Rheumatoid Arthritis
}}

{{PMID Auto GWAS
  |PMID=23455636
  |Trait=Age-related macular degeneration
  |Title=Seven new loci associated with age-related macular degeneration.
  |RiskAllele=A
  |Pval=2E-20
  |OR=1.30
  |ORtxt=[1.24-1.36]
  |OA=1
}}

{{PMID Auto
|PMID=24160669
|Title=Impact of APOE gene polymorphisms on the lipid profile in an Algerian population
}}

{{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=23286790
|Title=Genome-wide linkage analysis for human longevity: Genetics of Healthy Aging Study.
|OA=1
}}

{{PMID Auto
|PMID=24922540
|Title=Genetic Determinants of Long-Term Changes in Blood Lipid Concentrations: 10-Year Follow-Up of the GLACIER Study
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}