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 (fanxh@zju.edu.cn)

    Website using assistance : Leihong Wu (11019004@zju.edu.cn)



    Basic Information

    Gene Name: HMGCR

    Description: 3-hydroxy-3-methylglutaryl-Coenzyme A reductase

    Entrez Gene ID: 3156

    SwissProt Acc Number: P04035

    RefSeq: NM_000859

    It was suspected to be CHD related:

    ..HMGCR gene polymorphism is associated with stroke risk in the EPIC-Norfolk study...

    From PMID: 19923996, in Journal Eur J Cardiovasc Prev Rehabil. , 2010


    References

    There were 12 potential papers with HMGCR and CHD.

    PMIDTitleJournalsDetails
    23933271 The effects of age and gender on the relationship between HMGCR promoter-911 SNP (rs33761740) and serum lipids in patients with coronary heart disease.GeneMore Details
    22355267 An anti-PCSK9 antibody reduces LDL-cholesterol on top of a statin and suppresses hepatocyte SREBP-regulated genes.International journal of biological sciencesMore Details
    22654671 Knowledge-driven analysis identifies a gene-gene interaction affecting high-density lipoprotein cholesterol levels in multi-ethnic populations.PLoS geneticsMore Details
    21862702 "Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk."Journal of lipid researchMore Details
    21860704 Implications of discoveries from genome-wide association studies in current cardiovascular practice.World journal of cardiologyMore Details
    20578904 "Common variants of HMGCR, CETP, APOAI, ABCB1, CYP3A4, and CYP7A1 genes as predictors of lipid-lowering response to atorvastatin therapy."DNA and cell biologyMore Details
    19923996 HMGCR gene polymorphism is associated with stroke risk in the EPIC-Norfolk study.European journal of cardiovascular prevention and rehabilitation : officialMore Details
    19558216 A combination of proatherogenic single-nucleotide polymorphisms is associated with increased risk of coronary artery disease and myocardial infarction in Asian Indians.DNA and cell biologyMore Details
    20031582 Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort.Circulation. Cardiovascular geneticsMore Details
    18261733 "Genetic variation at the LDL receptor and HMG-CoA reductase gene loci, lipid levels, statin response, and cardiovascular disease incidence in PROSPER."AtherosclerosisMore Details
    18787507 Pharmacological effects of lipid-lowering drugs recapitulate with a larger amplitude the phenotypic effects of common variants within their target genes.Pharmacogenetics and genomicsMore Details
    15530894 Pharmacogenetics of HMG-CoA reductase inhibitors: exploring the potential for genotype-based individualization of coronary heart disease management.AtherosclerosisMore Details

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



    PPI interactions

    There were totally 11 unique genes interacted with HMGCR. Show PPI network

    Gene nameInteraction typereference PMIDCHD relation
    UBC Affinity Capture-Western17681147|15090540|14563840|19458199|20458442|21343306|22143767 No
    ERLIN2 Affinity Capture-Western21343306 No
    VCP Affinity Capture-Western21343306 No
    HMGCR in vitro10698924 CHD related
    STARD13 Two-hybrid14697242|14697242 No
    INSIG1 Affinity Capture-Western16168377|19458199|12535518 CHD related
    AMFR Affinity Capture-Western21343306 No
    RNF139 Affinity Capture-Western22143767 No
    DCUN1D1 Affinity Capture-MS21145461 No
    PRKACA in vitro;in vivo2369897 CHD related
    ARHGAP1 yeast 2-hybrid14697242 No


    Involved FDA drugs

    StatusDrubBank IDNameIndicationATC Code
    approved;nutraceuticalDB00157NADH"Some evidence suggests that NADH might be useful in treating Parkinson's disease, chronic fatigue syndrome, Alzheimer's disease and cardiovascular disease."
    approvedDB00175PravastatinFor the treatment of hypercholesterolemia and to reduce the risk of cardiovascular disease. C10AA03
    approvedDB00227Lovastatin"For management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia. For primary prevention of coronary heart disease and to slow progression of coronary atherosclerosis in patients with coronary heart disease. "C10AA02
    withdrawnDB00439CerivastatinUsed as an adjunct to diet for the reduction of elevated total and LDL cholesterol levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Types IIa and IIb) when the response to dietary restriction of saturated fat and cholesterol and other non-pharmacological measures alone has been inadequate.C10AA06
    approvedDB00641SimvastatinFor the treatment of hypercholesterolemia.C10AA01
    approvedDB01076Atorvastatin"May be used as primary prevention in individuals with multiple risk factors for coronary heart disease (CHD) and as secondary prevention in individuals with CHD to reduce the risk of myocardial infarction (MI), stroke, angina, and revascularization procedures. May be used to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). May be used in the treatment of primary hypercholesterolemia and mixed dyslipidemia, homozygous familial hypercholesterolemia, primary dysbetalipoproteinemia, and/or hypertriglyeridemia as an adjunct to dietary therapy to decrease serum total and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and triglyceride concentrations, while increasing high-density lipoprotein cholesterol (HDL-C) levels."C10AA05
    approvedDB01095Fluvastatin"To be used as an adjunct to dietary therapy to prevent cardiovascular events. May be used as secondary prevention in patients with coronary heart disease (CHD) to reduce the risk of requiring coronary revascularization procedures, for reducing progression of coronary atherosclerosis in hypercholesterolemic patients with CHD, and for the treatment of primary hypercholesterolemia and mixed dyslidipidemia. "C10AA04
    approvedDB01098Rosuvastatin"Used as an adjunct to dietary therapy to treat primary hypercholesterolemia (heterozygous familial and nonfamilial), mixed dyslipidemia and hypertriglyceridemia. Also indicated for homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies or when other such therapies are not available. "C10AA07
    experimentalDB01992Coenzyme A
    experimentalDB03169(S)-Hmg-Coa
    experimentalDB03431Adenosine-5'-Diphosphate
    experimentalDB034612'-Monophosphoadenosine 5'-Diphosphoribose
    experimentalDB043773-Hydroxy-3-Methyl-Glutaric Acid
    experimentalDB04447"1,4-Dithiothreitol"
    experimentalDB06693MevastatinNot used therapeutically due to its many side effects.
    experimentalDB06846"7-[3-(4-FLUORO-PHENYL)-1-ISOPROPYL-1H-INDOL-2-YL]-3,5-DIHYDROXY-HEPTANOIC ACID"