Rs7412

Orientation

plus

is a	snp
is	mentioned by
dbSNP	rs7412
PheGenI	rs7412
nextbio	rs7412
hapmap	rs7412
1000 genomes	rs7412
hgdp	rs7412
ensembl	rs7412
gopubmed	rs7412
geneview	rs7412
scholar	rs7412
google	rs7412
pharmgkb	rs7412
gwascentral	rs7412
openSNP	rs7412
23andMe	rs7412
23andMe all	rs7412
SNP Nexus
SNPshot	rs7412
SNPdbe	rs7412
MSV3d	rs7412

Gene

APOE

Chromosome

19

Orientation

plus

Position

45412079

Reference

GRCh37 37.1/131

Max Magnitude

0

Geno	Mag	Summary
(C;C)	0	more likely to gain weight if taking olanzapine
(C;T)		more likely to gain weight if taking olanzapine
(T;T)		normal

?	(C;C) (C;T) (T;T)	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	107741
Desc	APOE2 ISOFORMS
Variant	0001
Related	also

OMIM	107741
Desc	HYPERLIPOPROTEINEMIA, TYPE III, ASSOCIATED WITH APOE2-FUKUOKA
Variant	0019
Related	also

Neighbor	rs769455
Distance	39

Neighbor	rs28931579
Distance	414

OMIM	601367
Desc	STROKE, ISCHEMIC
Variant
Related	also

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

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

[PMID 19752398] Gene variants and pravastatin LDL lowering response in prosper

GWAS snp
PMID	[PMID 22331829]
Trait
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.
Risk Allele
P-val	2E-47
Odds Ratio	6.2000 None

GWAS snp
PMID	[PMID 22286219]
Trait
Title	Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
Risk Allele
P-val	3E-58
Odds Ratio	0.7500 None

ClinVar
Risk	rs7412(T;T)
Normal	rs7412(C;C)
Significance	5
Disease
ClinVar	info
Gene	APOE
CLNDBN
Reversed	0
CLNHGVS	NC_000019.9:g.45412079C>T
CLNSRC

[PMID 15113403] 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] Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

[PMID 16603077] Variation at APOE and STH loci and Alzheimer's disease.

[PMID 17048007] Association of warfarin dose with genes involved in its action and metabolism.

[PMID 17356695] Variation in GYS1 interacts with exercise and gender to predict cardiovascular mortality.

[PMID 17357073] 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] Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association.

[PMID 17456829] Evaluation of genetic factors for warfarin dose prediction.

[PMID 17658295] Association of ApoE genetic variants with obstructive sleep apnea in children.

[PMID 17672902] Subarachnoid hemorrhage: tests of association with apolipoprotein E and elastin genes.

[PMID 17903299] 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] Genetic determinants of basal C-reactive protein expression in Filipino systemic lupus erythematosus families.

[PMID 18254975] Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat.

[PMID 18275964] 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] APOE/C1/C4/C2 hepatic control region polymorphism influences plasma apoE and LDL cholesterol levels.

[PMID 18513389] New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background.

[PMID 18596683] Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.

[PMID 18603647] Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.

[PMID 18823527] A genome-wide association study for late-onset Alzheimer's disease using DNA pooling.

[PMID 18974842] Gender differences in genetic risk profiles for cardiovascular disease.

[PMID 18976728] Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE.

[PMID 19001172] Analyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci.

[PMID 19014573] Application of two machine learning algorithms to genetic association studies in the presence of covariates.

[PMID 19058936] A polymorphism of apolipoprotein E (APOE) gene is associated with age at natural menopause in Caucasian females.

[PMID 19118814] Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease.

[PMID 19131662] 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] Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.

[PMID 19285141] Genetic determinants of target and novelty-related event-related potentials in the auditory oddball response.

[PMID 19299407] Replication of genetic associations with plasma lipoprotein traits in a multiethnic sample.

[PMID 19336475] 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] Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease.

[PMID 19756043] A simple and efficient algorithm for genome-wide homozygosity analysis in disease.

[PMID 19787382] Introduction to the DISRUPT postprandial database: subjects, studies and methodologies.

[PMID 19802338] 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] Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.

[PMID 19936222] Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis.

[PMID 19951432] 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] Genetic variants involved in gallstone formation and capsaicin metabolism, and the risk of gallbladder cancer in Chilean women.

[PMID 20451875] Alzheimer's Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans.

[PMID 20565774] 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] 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] IQ, educational attainment, memory and plasma lipids: associations with apolipoprotein E genotype in 5995 children.

[PMID 21228733] 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] Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE.

[PMID 21647738] 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
APOE-R176C
aa_change	Arg176Cys
aa_change_short	R176C
impact	pharmacogenetic
qualified_impact	Insufficiently evaluated pharmacogenetic
overall_frequency	0.0678997
summary	This is generally known as the ApoE2 variant of ApoE and is associated with a decreased risk of Alzheimer's disease.

GWAS snp
PMID	[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.
Risk Allele
P-val	2E-9
Odds Ratio	12.30 [8.4-16.3] mg/dL decrease

[PMID 23050023] Association of genetic variants influencing lipid levels with coronary artery disease in Japanese individuals