Rs429358

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Orientationplus
is asnp
is mentioned by
dbSNPrs429358
PheGenIrs429358
nextbiors429358
hapmaprs429358
1000 genomesrs429358
hgdprs429358
ensemblrs429358
gopubmedrs429358
geneviewrs429358
scholarrs429358
googlers429358
pharmgkbrs429358
gwascentralrs429358
openSNPrs429358
23andMers429358
23andMe allrs429358
SNP Nexus

SNPshotrs429358
SNPdbers429358
MSV3drs429358
GeneAPOE
Chromosome19
Orientationplus
GMAF0.1492
Position44908684
ReferenceGRCh38 38.1/141
Max Magnitude1.2
Geno Mag Summary
(C;C) 1.2 one of 2 snps relevant to classifying APOE genotype
(C;T) >3x increased risk for Alzheimer's; 1.4x increased risk for heart disease
(T;T) 0 common
? (C;C) (C;T) (T;T) 28

This SNP, located in the fourth exon of the ApoE gene, affects the amino acid at position 130 of the resulting protein. The more common rs429358 allele is (T). If the allele is (C) and the same chromosome also harbors the rs7412(C) allele, the combination is known as an Apo-ε4 allele. The Apo-ε4 allele has a strong influence on the risk of Alzheimer's disease. Both deCODEme and 23andMe (v3 chip) test for this SNP.

Many studies have estimated the level of risk, and it varies depending on age, sex, ethnicity, and other factors. One meta-analysis estimated the odds ratios for homozygous rs429358(C;C) individuals compared to the more common ApoE3/ApoE3 homozygotes to be 12x for late-onset Alzheimer's and 61x for early-onset disease. [PMID 10325447]

Meta-analyses have also supported the association between the Apo-ε4 allele and somewhat increased risk for heart disease, with an odds ratio of 1.42 (CI: 1.26 - 1.61).[PMID 15488874]

Note: Although ApoE status is technically defined by these two SNPs, rs429358 and rs7412, a SNP in the adjacent ApoC1 gene, rs4420638, is co-inherited with ApoE and thus often - though not completely - predictive of it.

OMIM107741
DescHYPERLIPOPROTEINEMIA, TYPE III, AUTOSOMAL DOMINANT
Variant0008
Relatedalso
OMIM107741
DescALZHEIMER DISEASE 2
Variant0016
Relatedalso
OMIM107741
DescHYPERLIPOPROTEINEMIA, TYPE III, ASSOCIATED WITH APOE4
Variant0022
Relatedalso
Neighborrs28931577
Distance39
Neighborrs28931578
Distance67


Venter snp
Source plos
Gene APOE
allele C
frequency
sift TOLERATED
HuRef 1103691153316
Disease Association The APOE*4 allele is associated with late onset Alzheimer disease 2 (AD2) (MIM:104310). The APOE*4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE*4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known.



OMIM601367
DescSTROKE, ISCHEMIC
Variant
Relatedalso
[PMID 19818961OA-icon.png] Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm


GWAS snp
PMID [PMID 20100581OA-icon.png]
Trait Brain imaging
Title Whole Genome Association Study of Brain-Wide Imaging Phenotypes for Identifying Quantitative Trait Loci in MCI and AD: A Study of the ADNI Cohort
Risk Allele
P-val NS
Odds Ratio None None


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GWAS snp
PMID [PMID 21123754OA-icon.png]
Trait
Title Genome-wide association study of CSF biomarkers A{beta}1-42, t-tau, and p-tau181p in the ADNI cohort.
Risk Allele
P-val 0.000001
Odds Ratio None None


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ClinVar
Risk rs429358(C;C)
Alt rs429358(C;C)
Reference rs429358(T;T)
Significance 5
Disease Familial type 3 hyperlipoproteinemia, ALZHEIMER DISEASE 2, APOE4(-)-FREIBURG, APOE4 VARIANT
ClinVar info
Gene APOE
CLNDBN Familial type 3 hyperlipoproteinemia, ALZHEIMER DISEASE 2, DUE TO APOE4 ISOFORM, APOE4(-)-FREIBURG, APOE4 VARIANT
Reversed 0
CLNHGVS NC_000019.9:g.45411941T>C
CLNSRC GTR, OMIM Allelic Variant
CLNACC RCV000019438.27, RCV000019448.28, RCV000019455.26, RCV000019456.26, RCV000019458.22



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GET Evidence
APOE-C130R
aa_change Cys130Arg
aa_change_short C130R
impact pathogenic
qualified_impact High clinical importance, pathogenic
overall_frequency 0.135392
summary This is generally known as the ApoE4 allele of ApoE and is associated with increased risk of Alzheimer's. 20-25% of individuals are heterozygous for this variant, and 1-2% are homozygous. Data from Khachaturian et al. suggests an average 7% of all individuals developed Alzheimer's by the age of 80; when this is split by ApoE4 status: 10% of ApoE4 heterozygotes (3% increased attributable risk), 40% of ApoE4 homozygotes (33% increased attributable risk), and 5% of non-carriers (2% decreased attributable risk). Notably, their model suggests 70-75% of people would eventually develop Alzheimer's by the age of 100 regardless of ApoE4 genotype (and 25-30% are resistant, regardless of genotype), but that ApoE4 variants shift the disease onset to occur significantly earlier (4 years earlier for heterozygous carriers, 13 years for homozygotes).



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

GWAS snp
PMID [PMID 23419831]
Trait Alzheimer's disease biomarkers
Title APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study.
Risk Allele C
P-val 5E-14
Odds Ratio NR NR


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