{{Rsnum
|rsid=1799983
|Gene=NOS3
|Chromosome=7
|position=150999023
|Orientation=plus
|ReferenceAllele=T
|MissenseAllele=G
|GMAF=0.197
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(G;G)
|geno2=(G;T)
|geno3=(T;T)
|Gene_s=NOS3
}}{{ population diversity
| geno1=(G;G)
| geno2=(G;T)
| geno3=(T;T)
| CEU | 38.5 | 53.8 | 7.7
| HCB | 77.8 | 22.2 | 0.0
| JPT | 86.4 | 13.6 | 0.0
| YRI | 87.3 | 12.7 | 0.0
| ASW | 0.0 | 0.0 | 0.0
| CHB | 77.8 | 22.2 | 0.0
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=28
}}[[rs1799983]] (also known as Glu298Asp, E298D, or G894T) located in the [[NOS3]] gene was associated with an ~2x risk (p=0.006) of developing [[pre-eclampsia]] (pregnancy-induced [[hypertension]]) and further complications of it in a study of ~50 African women.{{PMID|16059745}}

A large meta-analysis combining 26 studies (9,867 patients) found that homozygosity for [[rs1799983]](T;T) increases risk of ischemic [[heart disease]]. The odds ratio was 1.31 (CI: 1.13-1.51).{{PMID|15007011}}

However, a study of 1,600 Greek patients concluded that [[rs1799983]] was not associated with risk of acute myocardial infarction in that population.{{PMID|18495009|OA=1
}}

{{PMID|19132956}} left ventricular hypertrophy in human essential hypertension OR=1.5

{{omim
|desc=CORONARY SPASMS, SUSCEPTIBILITY TO
|id=163729
|rsnum=1799983
|variant=0001
}}

{{PMID Auto
|PMID=19419976
|Title=Endothelial Nitric Oxide Synthase Tagging Single Nucleotide Polymorphisms and Recovery From Aneurysmal Subarachnoid Hemorrhage
|OA=1
}}
{{PMID Auto
|PMID=19435423
|Title=Lack of Association Between Matrix Metalloproteinase-9 and Endothelial Nitric Oxide Synthase Gene Polymorphisms and Coronary Artery Disease in Turkish Population
}}
{{PMID Auto
|PMID=19246226
|Title=The endothelial nitric oxide synthase gene and risk of diabetic nephropathy and development of cardiovascular disease in type 1 diabetes
}}

{{PMID Auto
|PMID=19815736
|Title=The Relation between Endothelial Nitric Oxide Synthase Gene Variants and Primary Open-Angle Glaucoma: Interactions with Gender and Postmenopausal Hormone Use
|OA=1
}}
{{PMID Auto
|PMID=19960019
|Title=Association of NOS3 Glu298Asp SNP with hypertension and possible effect modification of dietary fat intake in the ARIC study
|OA=1
}}

{{PMID Auto
|PMID=20409549
|Title=NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids
}}
{{PMID Auto
|PMID=20467051
|Title=Single Nucleotide Polymorphism (SNP) of Endothelial Nitric Oxide Synthase (eNOS) Gene (GLU298ASP Variant) in Infertile Men with Asthenozoospermia
}}
{{PMID Auto
|PMID=20565909
|Title=Frequency of eNOS polymorphisms in the Colombian general population
|OA=1
}}
{{PMID Auto
|PMID=20691505
|Title=NOS3 gene rs1799983 polymorphism and incident dementia in elderly stroke survivors
}}

{{PharmGKB
|RSID=rs1799983
|Name_s=NOS3:894G>T
|Gene_s=NOS3
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19671875
|Annotation=Risk or phenotype-associated allele: T. Phenotype: Women assigned to chemotherapy who had NOS3 &#8722;786 CC and 894 TT genotypes had an increased risk of recurrence compared with those with common alleles. Study size: 1153. Study population/ethnicity: Women with Breast Neoplasms receiving CMF (cyclophosphamide, methotrexate and fluorouracil) or CAF (cyclophosphamide, doxorubicin and fluorouracil) adjuvant therapy. Significance metric(s): HR = 2.32 (95% CI, 1.26-4.25); p = 0.008. Type of association: CO.
|Drugs=cyclophosphamide; doxorubicin; fluorouracil; methotrexate
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165291867
}}
{{PMID Auto
|PMID=21174581
|Title=Genetic Variants, Endothelial Function, and Risk of Preeclampsia Among American Indians
}}

{{PMID Auto
|PMID=21293869
|Title=Influence of endothelial nitric oxide synthase polymorphisms in psoriasis risk
}}
{{PMID Auto
|PMID=21291465
|Title=The association of genetic polymorphisms with cerebral palsy: a meta-analysis
}}

{{PMID Auto
|PMID=21886581
|Title=Genetic Association Analysis of NOS3 and Methamphetamine-Induced Psychosis Among Japanese
|OA=1
}}

{{PMID Auto
|PMID=21963893
|Title=Polymorphisms of genes in nitric oxide-forming pathway associated with ischemic stroke in Chinese Han population
}}

{{PMID Auto
|PMID=21968727
|Title=Association of eNOS gene polymorphisms with essential hypertension in the Han population in southwestern China
}}

{{PMID Auto
|PMID=22025889
|Title=Reproductive factors and NOS3 variant interactions in primary open-angle glaucoma
|OA=1
}}

{{PMID Auto
|PMID=22031268
|Title=Three polymorphisms of the eNOS gene and plasma levels of metabolites of nitric oxide in depressed Japanese patients: a preliminary report
}}

{{PMID Auto
|PMID=22207178
|Title=Lack of association between Glu298Asp polymorphism and coronary artery disease in North Indians
}}

{{PMID Auto
|PMID=22251423
|Title=NAMPT (visfatin) and AKT1 genetic variants associate with myocardial infarction
}}

{{PMID Auto
|PMID=22417945
|Title=The G894T polymorphism on endothelial nitric oxide synthase gene is associated with increased coronary heart disease among Asia population: Evidence from a Meta analysis
}}

{{ClinVar
|rsid=1799983
|Reversed=0
|FwdREF=T
|FwdALT=G
|REF=T
|ALT=G
|RSPOS=150696111
|CHROM=7
|GMAF=0.1964
|dbSNPBuildID=89
|SSR=0
|SAO=1
|VP=0x05037800000017051f110100
|GENEINFO=NOS3:4846
|GENE_NAME=NOS3
|GENE_ID=4846
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000007.13:g.150696111T>G
|CLNORIGIN=1
|CLNSIG=255
|Tags=PM;TPA;PMC;S3D;SLO;VLD;G5A;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.197; 0.803
|CLNACC=RCV000015053.1; RCV000015054.1; RCV000015055.1; RCV000015056.24; RCV000015057.1; RCV000015058.1
|CLNDBN=Coronary artery spasm 1, susceptibility to; Alzheimer disease, late-onset, susceptibility to; Hypertension, pregnancy-induced, susceptibility to; Hypertension resistant to conventional therapy; Ischemic heart disease, susceptibility to; Ischemic stroke, susceptibility to
|CLNDSDB=MedGen
|CLNDSDBID=C1834153; C1834154; C1834155
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=163729.0001
|COMMON=1
|Disease=Coronary artery spasm 1; Alzheimer disease; Hypertension; Hypertension resistant to conventional therapy; Ischemic heart disease; Ischemic stroke
}}

{{PMID Auto
|PMID=15500681
|Title=Detecting imbalanced expression of SNP alleles by minisequencing on microarrays.
|OA=1
}}

{{PMID Auto
|PMID=15726497
|Title=Gene-environment interaction effects on the development of immune responses in the 1st year of life.
|OA=1
}}

{{PMID Auto
|PMID=16820586
|Title=Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.
|OA=1
}}

{{PMID Auto
|PMID=17101543
|Title=Glu298Asp and NOS4ab polymorphisms in diabetic nephropathy.
}}

{{PMID Auto
|PMID=17107626
|Title=Comparison of PrASE and Pyrosequencing for SNP Genotyping.
|OA=1
}}

{{PMID Auto
|PMID=17404185
|Title=Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study.
}}

{{PMID Auto
|PMID=17579350
|Title=NOS-I and -III gene variants are differentially associated with facets of suicidal behavior and aggression-related traits.
}}

{{PMID Auto
|PMID=17601350
|Title=A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition.
|OA=1
}}

{{PMID Auto
|PMID=17605790
|Title=Lack of association between endothelial nitric oxide synthase (NOS3) gene polymorphisms and suicide attempts.
|OA=1
}}

{{PMID Auto
|PMID=17717598
|Title=Discovery of common human genetic variants of GTP cyclohydrolase 1 (GCH1) governing nitric oxide, autonomic activity, and cardiovascular risk.
|OA=1
}}

{{PMID Auto
|PMID=17980690
|Title=Polymorphisms in the endothelial nitric oxide synthase gene and bone density/ultrasound and geometry in humans.
|OA=1
}}

{{PMID Auto
|PMID=18069999
|Title=Renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms are not associated with the risk of incident type 2 diabetes mellitus: a prospective cohort study.
}}

{{PMID Auto
|PMID=18194558
|Title=A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples.
|OA=1
}}

{{PMID Auto
|PMID=18246059
|Title=Habitual energy expenditure modifies the association between NOS3 gene polymorphisms and blood pressure.
|OA=1
}}

{{PMID Auto
|PMID=18279468
|Title=Ten renin-angiotensin system-related gene polymorphisms in maximally treated Canadian Caucasian patients with heart failure.
|OA=1
}}

{{PMID Auto
|PMID=18349107
|Title=Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis.
}}

{{PMID Auto
|PMID=18482449
|Title=Investigating the complex genetic architecture of ankle-brachial index, a measure of peripheral arterial disease, in non-Hispanic whites.
|OA=1
}}

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

{{PMID Auto
|PMID=18622260
|Title=Common genetic variation in six lipid-related and statin-related genes, statin use and risk of incident nonfatal myocardial infarction and stroke.
|OA=1
}}

{{PMID Auto
|PMID=18663495
|Title=Nitric oxide synthase genes and their interactions with environmental factors in Parkinson's disease.
|OA=1
}}

{{PMID Auto
|PMID=18676870
|Title=Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China.
|OA=1
}}

{{PMID Auto
|PMID=18682580
|Title=Oxidative response gene polymorphisms and risk of adult brain tumors.
|OA=1
}}

{{PMID Auto
|PMID=18687083
|Title=Lack of association of endothelial nitric oxide synthase polymorphisms and migraine.
}}

{{PMID Auto
|PMID=18698212
|Title=Association of renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms with blood pressure progression and incident hypertension: prospective cohort study.
|OA=1
}}

{{PMID Auto
|PMID=18698231
|Title=Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.
|OA=1
}}

{{PMID Auto
|PMID=18776599
|Title=Susceptibility genes for gentamicin-induced vestibular dysfunction.
|OA=1
}}

{{PMID Auto
|PMID=18805939
|Title=Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis.
|OA=1
}}

{{PMID Auto
|PMID=18936436
|Title=Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
|OA=1
}}

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

{{PMID Auto
|PMID=19168583
|Title=Nitric oxide synthase gene polymorphisms and prostate cancer risk.
|OA=1
}}

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

{{PMID Auto
|PMID=19330901
|Title=Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.
|OA=1
}}

{{PMID Auto
|PMID=19505917
|Title=Lead exposure, polymorphisms in genes related to oxidative stress, and risk of adult brain tumors.
|OA=1
}}

{{PMID Auto
|PMID=19559392
|Title=A candidate gene association study of 77 polymorphisms in migraine.
|OA=1
}}

{{PMID Auto
|PMID=19587357
|Title=A systematic meta-analysis of genetic association studies for diabetic retinopathy.
|OA=1
}}

{{PMID Auto
|PMID=19729601
|Title=Candidate gene polymorphisms for ischemic stroke.
|OA=1
}}

{{PMID Auto
|PMID=20204503
|Title=The association between two polymorphisms of eNOS and breast cancer risk: a meta-analysis.
}}

{{PMID Auto
|PMID=20346360
|Title=Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease.
|OA=1
}}

{{PMID Auto
|PMID=20367485
|Title=A variant of the endothelial nitric oxide synthase gene (NOS3) associated with AMS susceptibility is less common in the Quechua, a high altitude Native population.
}}

{{PMID Auto
|PMID=20406163
|Title=Fenofibrate and metabolic syndrome.
}}

{{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=20445800
|Title=Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy.
|OA=1
}}

{{PMID Auto
|PMID=20457799
|Title=Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia.
}}

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

{{PMID Auto
|PMID=20624112
|Title=Tamm-Horsfall protein gene is associated with distal tubular dysfunction in patients with type 1 diabetes.
}}

{{PMID Auto
|PMID=20811626
|Title=Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer.
|OA=1
}}

{{PMID Auto
|PMID=21252862
|Title=NOS3 variants, physical activity, and blood pressure in the European Youth Heart Study.
}}

{{PMID Auto
|PMID=21332392
|Title=Endothelial nitric oxide synthase haplotypes associated with aura in patients with migraine.
}}

{{PMID Auto
|PMID=21577011
|Title=NCAM1, TACR1 and NOS genes and temperament: a study on suicide attempters and controls.
}}

{{PMID Auto
|PMID=21613201
|Title=The effect of maternal and fetal beta2-adrenoceptor and nitric oxide synthase genotype on vasopressor requirement and fetal acid-base status during spinal anesthesia for cesarean delivery.
|OA=1
}}

{{PMID Auto
|PMID=21674837
|Title=Association of NOS3 tag polymorphisms with hypoxic-ischemic encephalopathy.
|OA=1
}}

{{PMID Auto
|PMID=21703358
|Title=Polymorphisms in nitric-oxide synthase 3 may influence the risk of urinary-bladder cancer.
}}

{{PMID Auto
|PMID=22064666
|Title=Endothelial nitric oxide synthase genotypes and haplotypes modify the responses to sildenafil in patients with erectile dysfunction.
}}

{{PMID Auto
|PMID=22588838
|Title=The apoptosis pathway and the genetic predisposition to Achilles tendinopathy.
}}

{{PMID Auto
|PMID=22676277
|Title=Vascular associated gene variants in patients with preeclampsia: results from the Danish National Birth Cohort
}}

{{GET Evidence
|gene=NOS3
|aa_change=Asp298Glu
|aa_change_short=D298E
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs1799983
|overall_frequency_n=8047
|overall_frequency_d=10742
|overall_frequency=0.749116
|n_genomes=52
|n_genomes_annotated=0
|n_haplomes=86
|n_articles=1
|n_articles_annotated=1
|gene_in_genetests=Y
|in_pharmgkb=Y
|nblosum100=-2
|autoscore=2
|webscore=N
|n_web_uneval=8
}}

{{PMID Auto
|PMID=22919264
|Title=No difference in genotype frequencies of polymorphisms of the nitric oxide pathway between Caucasian normal and high tension glaucoma patients
|OA=1
}}

{{PMID Auto
|PMID=23269619
|Title=Association of endothelial nitric oxide synthase gene polymorphisms with classical risk factors in development of premature coronary artery disease
}}

{{PMID Auto
|PMID=23276910
|Title=Association between polymorphism of the NQO1, NOS3 and NFE2L2 genes and AMD
}}

{{PMID Auto
|PMID=23387538
|Title=Influence of Endothelial Nitric Oxide Synthase Gene Polymorphisms (-786T/C, 4a4b, 894G/T) on Iranian Kidney Transplant Recipients
}}

{{PMID Auto
|PMID=23512673
|Title=More severe clinical course of cardiovascular dysfunction in intensive care unit patients with the 894TT eNOS genotype
}}

{{PMID Auto
|PMID=23603420
|Title=Polymorphisms of Angiotensin converting enzyme and nitric oxide synthase 3 genes as risk factors of high-altitude pulmonary edema: a case-control study and meta-analysis
}}

{{PMID Auto
|PMID=23681449
|Title=Genes for Elite Power and Sprint Performance: ACTN3 Leads the Way
}}

{{PMID Auto
|PMID=23922896
|Title=Genetic Polymorphism of NOS3 with Susceptibility to Deep Vein Thrombosis after Orthopedic Surgery: A Case-Control Study in Chinese Han Population
|OA=1
}}

{{PMID Auto
|PMID=24035903
|Title=The -974 C&gt;A (rs3087459) gene polymorphism in the endothelin gene (EDN1) is associated with risk of developing acute coronary syndrome in Mexican patients
}}

{{PMID Auto
|PMID=24213141
|Title=A susceptibility haplotype within the endothelial nitric oxide synthase gene influences bone mineral density in hypertensive women
}}

{{PMID Auto
|PMID=24602444
|Title=Analysis of nitric oxide synthase gene polymorphisms in neonatal respiratory distress syndrome among the Chinese Han population
|OA=1
}}

{{PMID Auto
|PMID=22729570
|Title=AKT3, ANGPTL4, eNOS3, and VEGFA associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau.
}}

{{PMID Auto
|PMID=22865486
|Title=Interaction among nitric oxide (NO)-related genes in migraine susceptibility.
}}

{{PMID Auto
|PMID=22982457
|Title=eNOS gene polymorphisms modify the association of PM(10) with oxidative stress.
}}

{{PMID Auto
|PMID=23062210
|Title=eNOS tag SNP haplotypes in hypertensive disorders of pregnancy.
}}

{{PMID Auto
|PMID=23107763
|Title=Host genetic risk factors for community-acquired pneumonia.
}}

{{PMID Auto
|PMID=23176758
|Title=Association of nitric oxide synthase gene polymorphisms (-786T>C, 4a4b, 894G>T) with primary ovarian insufficiency in Korean women.
}}

{{PMID Auto
|PMID=23333443
|Title=Analysis of polymorphisms and haplotypes in genes associated with vascular tone, hypertension and oxidative stress in Mexican-Mestizo women with severe preeclampsia.
}}

{{PMID Auto
|PMID=23560644
|Title=Polymorphisms in genes involved in the free-radical process in patients with sudden sensorineural hearing loss and Meniere's disease.
}}

{{PMID Auto
|PMID=23563728
|Title=Association of endothelial nitric oxide synthase gene polymorphisms with type 2 diabetes mellitus: a meta-analysis.
}}

{{PMID Auto
|PMID=23775455
|Title=Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus.
}}

{{PMID Auto
|PMID=24047197
|Title=Endothelial nitric oxide synthase gene variants and haplotypes associated with an increased risk of idiopathic recurrent miscarriage
}}

{{PMID Auto
|PMID=24756758
|Title=Association of endothelia nitric oxide synthase gene rs1799983 polymorphism with susceptibility to prostate cancer: a meta-analysis
}}

{{PMID Auto
|PMID=24870799
|Title=Nitric oxide synthase 3 gene variants and colorectal cancer: a meta-analysis
}}

{{PMID Auto
|PMID=24085449
|Title=Polymorphisms in the endothelial nitric oxide synthase gene associated with recurrent miscarriage
}}

{{PMID Auto
|PMID=24938467
|Title=Genetic variants of the endothelial NO synthase gene (eNOS) may confer increased risk of sporadic congenital heart disease
}}

{{PMID Auto
|PMID=24940036
|Title=Endothelial nitric oxide synthase polymorphisms and susceptibility to high-tension primary open-angle glaucoma in an Egyptian cohort
}}

{{PMID Auto
|PMID=24972130
|Title=Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}