How to Build CHD@ZJU

CHD related Articles were retrieved from Pubmed, by entering keywords "coronary heart disease" and constrict the publish date from 2000/1/1 to now (2013/1/23). As a result, totally 115898 articles were found and their abstracts were downloaded for text mining. Since some articles didn't contain abstracts, only 88396 abstracts remained.

The text-mining process to get CHD related genes could be divided in to 5 following steps:

  • 1) Extracting all keywords from abstracts and ignoring those keywords start with numbers. 101402 keywords were extracted.

  • 2) Input these keywords into Gene library in ArrayTrack and find possible related genes. 4674 genes were then found.

  • 3) Put these 4674 genes again into pubmed abstracts to find related aticles. Only genes which offical name or there keyword description (such as prolactin for gene PRL) could be found in the abstract would be remained. As a result, 1247 genes were remained.

  • 4) Manually examined on the 1247 genes to validate it was acutally related to CHD. Some genes would be filtered if it represents other meanings (such as gene CAD, Entrez ID:790, carbamoyl-phosphate synthetase 2, is mostly meant coronary arterial disease in articles). 681 genes were then validated with at least one reference.

  • 5) All genes was compared with 1078 CHD genes in RGD database, and 370 genes were overlapped. These 370 genes were labels as "RGD_Supported" and the other 293 genes were labels as "REFERED". All 663 genes had supported references in CHD@ZJU which were examined by step 4.
  • How To contact Us

    Collaboration Information: Prof. Xiaohui Fan (

    Website using assistance : Leihong Wu (

    Basic Information

    Gene Name: NOS3

    Description: nitric oxide synthase 3 (endothelial cell)

    Entrez Gene ID: 4846

    SwissProt Acc Number: P29474

    RefSeq: NM_000603

    It was suspected to be CHD related:

    ..We observed significant associations with NOS3 variants and CHD and heart failure and significant pharmacogenetic effects for stroke and all cause mortality..

    From PMID: 22470539, in Journal PLoS One , 2012


    There were 43 potential papers with NOS3 and CHD.

    24068186 Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease.Basic research in cardiologyMore Details
    24302629 A novel truncated form of eNOS associates with altered vascular function.Cardiovascular researchMore Details
    23918902 Association between endothelial nitric oxide synthase gene polymorphism (-786T>C) and interleukin-6 in acute coronary syndrome.Human & experimental toxicologyMore Details
    23397596 Endothelial NOS (NOS3) impairs myocardial function in developing sepsis.Basic research in cardiologyMore Details
    23048191 Nitric oxide synthase-3 deficiency results in hypoplastic coronary arteries and postnatal myocardial infarction.European heart journalMore Details
    22652373 Association between endothelial nitric oxide gene intron 4a4b VNTR polymorphism and plasma homocysteine concentrations in Tunisian male patients with myocardial infarction."Nutrition research (New York, N.Y.)"More Details
    22388798 Gene panels to help identify subgroups at high and low risk of coronary heart disease among those randomized to antihypertensive treatment: the GenHAT study.Pharmacogenetics and genomicsMore Details
    22682929 Association of plasma nitric oxide concentration and endothelial nitric oxide synthase T-786C gene polymorphism in coronary artery disease.Pathophysiology : the official journal of the International Society forMore Details
    22579300 NOing the heart: role of nitric oxide synthase-3 in heart development.Differentiation; research in biological diversityMore Details
    22475779 "Interaction between endothelial nitric oxide synthase gene polymorphisms (-786T>C, 894G>T and intron 4 a/b) and cardiovascular risk factors in acute coronary syndromes."Archives of medical researchMore Details
    23157875 Strong interaction between T allele of endothelial nitric oxide synthase with B1 allele of cholesteryl ester transfer protein TaqIB highly elevates the risk of coronary artery disease and type 2 diabetes mellitus.Human genomicsMore Details
    22470539 Pharmacogenetic association of NOS3 variants with cardiovascular disease in patients with hypertension: the GenHAT study.PloS oneMore Details
    22984364 A Multinomial Ordinal Probit Model with Singular Value Decomposition Method for a Multinomial Trait.Journal of probability and statisticsMore Details
    21816783 NOS3 Glu298Asp polymorphism interacts with virgin olive oil phenols to determine the postprandial endothelial function in patients with the metabolic syndrome.The Journal of clinical endocrinology and metabolismMore Details
    21194529 Association between -786TC polymorphism in the endothelial nitric oxide synthase gene and hypertension in the Tunisian population.Experimental and molecular pathologyMore Details
    23961079 Correlation and Identification of Variable number of Tandem repeats of eNOS Gene in Coronary artery disease (CAD).Saudi journal of biological sciencesMore Details
    20103956 Endothelial nitric oxide synthase gene Glu298Asp polymorphism in patients with coronary artery disease.Annals of Saudi medicineMore Details
    19931521 Polymorphisms of the NOS3 gene in Southern Chilean subjects with coronary artery disease and controls.Clinica chimica acta; international journal of clinical chemistryMore Details
    19407804 "Genetic and pharmacogenetic associations between NOS3 polymorphisms, blood pressure, and cardiovascular events in hypertension."American journal of hypertensionMore Details
    19691831 "Gene polymorphisms in APOE, NOS3, and LIPC genes may be risk factors for cardiac adverse events after primary CABG."Journal of cardiothoracic surgeryMore Details
    19407362 Metabolic background determines the importance of NOS3 polymorphisms in restenosis after percutaneous coronary intervention: A study in patients with and without the metabolic syndrome.Disease markersMore Details
    18818404 Inducible nitric oxide synthase expression and cardiomyocyte dysfunction during sustained moderate ischemia in pigs.Circulation researchMore Details
    18349107 Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis.American journal of physiology. Endocrinology and metabolismMore Details
    18398337 Vascular stiffness is related to superoxide generation in the vessel wall.Journal of hypertensionMore Details
    17927970 -786T>C polymorphism of the endothelial nitric oxide synthase gene in Chilean subjects with coronary artery disease and controls.Clinica chimica acta; international journal of clinical chemistryMore Details
    18463668 Endothelium-dependent vasodilation in conduit and resistance vessels in relation to the endothelial nitric oxide synthase gene.Journal of human hypertensionMore Details
    18343196 Tissue kallikrein deficiency aggravates cardiac remodelling and decreases survival after myocardial infarction in mice.European journal of heart failureMore Details
    17403027 The use of meta-analysis risk estimates for candidate genes in combination to predict coronary heart disease risk.Annals of human geneticsMore Details
    17903303 Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study.BMC medical geneticsMore Details
    16979000 The T(-786)C endothelial nitric oxide synthase genotype predicts cardiovascular mortality in high-risk patients.Journal of the American College of CardiologyMore Details
    16616056 Endothelial nitric oxide synthase G894T gene polymorphism in Chilean subjects with coronary artery disease and controls.Clinica chimica acta; international journal of clinical chemistryMore Details
    17009241 The -786C/T single-nucleotide polymorphism in the promoter of the gene for endothelial nitric oxide synthase: insensitivity to physiologic stimuli as a risk factor for rheumatoid arthritis.Arthritis and rheumatismMore Details
    17018701 Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease: a HuGE review.American journal of epidemiologyMore Details
    16492203 Association analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: the Diabetes Heart Study.Diabetic medicine : a journal of the British Diabetic AssociationMore Details
    16705470 Expression of nitric oxide related enzymes in coronary heart disease.Basic research in cardiologyMore Details
    17108813 "NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: the Atherosclerosis Risk in Communities study."Pharmacogenetics and genomicsMore Details
    15626780 Fetal origins of adult vascular dysfunction in mice lacking endothelial nitric oxide synthase."American journal of physiology. Regulatory, integrative and comparative"More Details
    16296949 Physiogenomic analysis links serum creatine kinase activities during statin therapy to vascular smooth muscle homeostasis.PharmacogenomicsMore Details
    15699455 Hypertension genes are genetic markers for insulin sensitivity and resistance.HypertensionMore Details
    15563531 Rosuvastatin reduces experimental left ventricular infarct size after ischemia-reperfusion injury but not total coronary occlusion.American journal of physiology. Heart and circulatory physiologyMore Details
    14510775 From molecules to mammals: what's NOS got to do with it?Acta physiologica ScandinavicaMore Details
    12825146 Genetic risk factors for erectile dysfunction and genetic determinants of drug response--on the way to improve drug safety?HerzMore Details
    11485372 Association between the NOS3 (-786 T/C) and the ACE (I/D) DNA genotypes and early coronary artery disease.Nitric oxide : biology and chemistry / official journal of the Nitric OxideMore Details

    NOTEs: These result is mostly from TEXT-MINING and there might have mismatches.

    PPI interactions

    There were totally 49 unique genes interacted with NOS3. Show PPI network

    Gene nameInteraction typereference PMIDCHD relation
    NOSTRIN Two-hybrid12446846|12446846 No
    CALM1 Affinity Capture-Western20705923|11397791 No
    CAMK2A Affinity Capture-Western11397791 CHD related
    NOS3 Two-hybrid11149895|12437348,9516116 CHD related
    AKT1 Affinity Capture-Western11425855 CHD related
    APP Affinity Capture-Western21163940|21163940 No
    CDC37 Affinity Capture-Western21163940|21163940 No
    ST13 Affinity Capture-Western21163940|21163940 No
    ELAVL3 Two-hybrid21163940 No
    PI4K2A Two-hybrid21163940 No
    ELAVL1 Two-hybrid21163940 No
    KANK2 Two-hybrid21163940 No
    RNF32 Two-hybrid21163940 No
    CEP55 Two-hybrid21163940 No
    EXOSC1 Two-hybrid21163940 No
    PAXIP1 Two-hybrid21163940 No
    PSEN2 Two-hybrid21163940 No
    EFEMP1 Two-hybrid21163940 No
    FIS1 Two-hybrid21163940 No
    EFEMP2 Two-hybrid21163940 No
    RNF31 Two-hybrid21163940 No
    UMPS Two-hybrid21163940 No
    IMMT Two-hybrid21163940 No
    MPRIP Two-hybrid21163940 No
    HTRA1 Two-hybrid21163940 No
    TXNDC11 Two-hybrid21163940 No
    ACTN2 Two-hybrid21163940 No
    ACTN4 Two-hybrid21163940 No
    H3F3A Two-hybrid21163940 No
    TECR Two-hybrid21163940 No
    BDKRB2 in vitro10681501,10510297 CHD related
    BDNF in vitro10493752 CHD related
    AGTR1 in vitro10510297 CHD related
    HSP90AA1 Affinity Capture-Western12676772|11744239|11744239|12124224|11988487|11425855 CHD related
    GUCY1B3 Reconstituted Complex12676772|12676772 CHD related
    CAV1 Affinity Capture-Western8910295|11425855|8910295 CHD related
    HDAC3 Affinity Capture-Western20705923 CHD related
    UBC Affinity Capture-MS21906983 No
    NOSIP Affinity Capture-Western16135813|11149895|11149895|11149895 No
    GCDH Affinity Capture-Western21163940 No
    A2M Two-hybrid21163940 No
    EXOC6 Two-hybrid21163940 No
    MAST1 Two-hybrid21163940 No
    APOE Two-hybrid21163940 CHD related
    PSEN1 Two-hybrid21163940 No
    NMT1 in vivo7512951 No
    SP1 in vitro;in vivo7541039 No
    PPP2R5A in vivo12501214,11397791 No
    EDNRB in vitro10510297 CHD related

    Involved FDA drugs

    StatusDrubBank IDNameIndicationATC Code
    approved;nutraceuticalDB00125L-Arginine"Used for nutritional supplementation, also for treating dietary shortage or imbalance."B05XB01
    approved;nutraceuticalDB00155L-Citrulline"Used for nutritional supplementation, also for treating dietary shortage or imbalance."
    approvedDB00360TetrahydrobiopterinFor the treatment of tetrahydrobiopterin (BH4) deficiency.A16AX07
    approvedDB01110Miconazole"For topical application in the treatment of tinea pedis (athlete’s foot), tinea cruris, and tinea corporis caused by <i>Trichophyton rubrum</i>, <i>Trichophyton mentagrophytes</i>, and <i>Epidermophyton floccosum</i>, in the treatment of cutaneous candidiasis (moniliasis), and in the treatment of tinea versicolor."A01AB09;A07AC01;D01AC02;G01AF04;J02AB01;S02AA13
    experimentalDB01821"L-N(Omega)-Nitroarginine-2,4-L-Diaminobutyric Amide"
    experimentalDB01833L-2-Amino-4-(Guanidinooxy)Butyric Acid
    experimentalDB02077L-N(Omega)-Nitroarginine-(4r)-Amino-L-Proline Amide
    experimentalDB02692"(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin"
    experimentalDB02994Hydroxydimethylarsine Oxide