Rs429358

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 ApoE4 allele. The ApoE4 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 ApoE4 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.

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.

[PMID 19818961] Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm

GWAS snp
PMID	[PMID 20100581]
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

[PMID 20406466] Genetic variants associated with fasting blood lipids in the U.S. population: Third National Health and Nutrition Examination Survey

[PMID 20429872] Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

[PMID 20822524] Isoform of APOE with retained intron 3; quantitation and identification of an associated single nucleotide polymorphism

[PMID 20946940] Association of variants within APOE; SORL1; RUNX1; BACE1 and ALDH18A1 with dementia in Alzheimer's disease in subjects with Down syndrome

[PMID 21263195] An APOE Haplotype Associated with Decreased ?4 Expression Increases the Risk of Late Onset Alzheimer's Disease

GWAS snp
PMID	[PMID 21123754]
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

[PMID 22174202] Apolipoprotein E Gene Polymorphisms Are Strong Predictors of Inflammation and Dyslipidemia in Rheumatoid Arthritis