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: PCSK9

    Description: proprotein convertase subtilisin/kexin type 9

    Entrez Gene ID: 255738

    SwissProt Acc Number: Q8NBP7

    RefSeq: NM_174936

    It was suspected to be CHD related:

    .."This study identifies the residues, sequence segments and surface patches of PCSK9 that are under strong purifying selection and provides important information for future studies of PCSK9 mutants and for investigations on the function of this regulator of cholesterol homeostasis."..

    From PMID: 18631360, in Journal FEBS J , 2008


    References

    There were 97 potential papers with PCSK9 and CHD.

    PMIDTitleJournalsDetails
    23932901 Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical update."Nutrition, metabolism, and cardiovascular diseases : NMCD"More Details
    23907036 The extended abnormalities in lipoprotein metabolism in familial hypercholesterolemia: developing a new framework for future therapies.International journal of cardiologyMore Details
    24161333 "AMG 145, A Monoclonal Antibody Against PCSK9, Facilitates Achievement of NCEP-ATP III LDL-C Goals Among High Risk Patients: An Analysis From the LAPLACE-TIMI 57 Trial."Journal of the American College of CardiologyMore Details
    24094767 "Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial."LancetMore Details
    24234650 Novel functional APOB mutations outside LDL-binding region causing familial hypercholesterolaemia.Human molecular geneticsMore Details
    24251769 LDL-c linked SNPs are associated with LDL-c and myocardial infarction despite lipid-lowering therapy in patients with established vascular disease.European journal of clinical investigationMore Details
    24252255 An Antibody against the C-Terminal Domain of PCSK9 Lowers LDL Cholesterol Levels InVivo.Journal of molecular biologyMore Details
    24243630 Molecular Lipids Identify Cardiovascular Risk and Are Efficiently Lowered by Simvastatin and PCSK9 Deficiency.The Journal of clinical endocrinology and metabolismMore Details
    23333725 Plasma proprotein convertase subtilisin kexin type 9 levels are related to markers of cholesterol synthesis in familial combined hyperlipidemia."Nutrition, metabolism, and cardiovascular diseases : NMCD"More Details
    23642322 Emerging LDL therapies: Using human genetics to discover new therapeutic targets for plasma lipids.Journal of clinical lipidologyMore Details
    23433768 Comparison of effects of pitavastatin versus pravastatin on serum proprotein convertase subtilisin/kexin type 9 levels in statin-naive patients with coronary artery disease.The American journal of cardiologyMore Details
    23997648 Autosomal dominant hypercholesterolemia: needs for early diagnosis and cascade screening in the tunisian population.Current genomicsMore Details
    23380588 Association between PCSK9 and LDLR gene polymorphisms with coronary heart disease: case-control study and meta-analysis.Clinical biochemistryMore Details
    23702357 Impactful clinical trials of 2012: what clinicians need to know.The Canadian journal of cardiologyMore Details
    23666884 Diagnosis and management of familial dyslipoproteinemias.Current cardiology reportsMore Details
    23578522 The next generation of novel low-density lipoprotein cholesterol-lowering agents: proprotein convertase subtilisin/kexin 9 inhibitors.Pharmacological research : the official journal of the Italian PharmacologicalMore Details
    23406852 [Targets of anti-hyperlipidemia drugs].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University.More Details
    23300213 PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population.Journal of lipid researchMore Details
    23375686 Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.AtherosclerosisMore Details
    23553812 Evaluation of proprotein convertase subtilisin/kexin type 9: focus on potential clinical and therapeutic implications for low-density lipoprotein cholesterol lowering.PharmacotherapyMore Details
    23844374 Porcine models of accelerated coronary atherosclerosis: role of diabetes mellitus and hypercholesterolemia.Journal of diabetes researchMore Details
    24135527 Genetic susceptibility for ischemic infarction and arteriolosclerosis based on neuropathologic evaluations."Cerebrovascular diseases (Basel, Switzerland)"More Details
    24115837 The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol."Drug design, development and therapy"More Details
    22923420 Pooled DNA resequencing of 68 myocardial infarction candidate genes in French canadians.Circulation. Cardiovascular geneticsMore Details
    23054246 Use of targeted exome sequencing as a diagnostic tool for Familial Hypercholesterolaemia.Journal of medical geneticsMore Details
    22892323 Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease.AtherosclerosisMore Details
    22883975 Genetic analysis of familial hypercholesterolaemia in Western Australia.AtherosclerosisMore Details
    22575316 Plasma PCSK9 levels and clinical outcomes in the TNT (Treating to New Targets) trial: a nested case-control study.Journal of the American College of CardiologyMore Details
    22244043 Molecular characterization of familial hypercholesterolemia in Spain.AtherosclerosisMore Details
    22408029 Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia.European heart journalMore Details
    22460556 Common and low-frequency genetic variants in the PCSK9 locus influence circulating PCSK9 levels."Arteriosclerosis, thrombosis, and vascular biology"More Details
    22228254 Screening for familial hypercholesterolaemia.PathologyMore Details
    22017319 Management of familial hypercholesterolaemia in children and adolescents.Journal of paediatrics and child healthMore Details
    23128163 Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial.JAMA : the journal of the American Medical AssociationMore Details
    22111029 Premature coronary artery disease and familial hypercholesterolemia: need for early diagnosis and cascade screening in the Indian population.Cardiology research and practiceMore Details
    23226021 Mipomersen and other therapies for the treatment of severe familial hypercholesterolemia.Vascular health and risk managementMore 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
    22848640 Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation.PloS oneMore 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
    21619378 The role of proprotein convertase subtilisin/kexin type 9 in hyperlipidemia: focus on therapeutic implications."American journal of cardiovascular drugs : drugs, devices, and other"More Details
    21860704 Implications of discoveries from genome-wide association studies in current cardiovascular practice.World journal of cardiologyMore Details
    21657943 "Familial hypercholesterolemia: epidemiology, Neolithic origins and modern geographic distribution."Critical reviews in clinical laboratory sciencesMore Details
    22152955 Genetic susceptibility to coronary heart disease in type 2 diabetes: 3 independent studies.Journal of the American College of CardiologyMore Details
    21872251 A novel type of familial hypercholesterolemia: double heterozygous mutations in LDL receptor and LDL receptor adaptor protein 1 gene.AtherosclerosisMore Details
    21633520 Cascade Screening for Familial Hypercholesterolemia (FH).PLoS currentsMore Details
    22216278 Large scale association analysis identifies three susceptibility loci for coronary artery disease.PloS oneMore Details
    20828696 Update of the Portuguese Familial Hypercholesterolaemia Study.AtherosclerosisMore Details
    20849207 Strategies for proprotein convertase subtilisin kexin 9 modulation: a perspective on recent patents.Expert opinion on therapeutic patentsMore Details
    20699424 Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population.Journal of lipid researchMore Details
    20144596 Moderate phenotypic expression of familial hypercholesterolemia in Tunisia.Clinica chimica acta; international journal of clinical chemistryMore Details
    20018285 Pseudoxanthoma elasticum and familial hypercholesterolemia: a deleterious combination of cardiovascular risk factors.AtherosclerosisMore Details
    20227438 Molecular pathways and agents for lowering LDL-cholesterol in addition to statins.Pharmacology & therapeuticsMore Details
    20172854 A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake.The Journal of biological chemistryMore Details
    19635789 Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route.The Journal of biological chemistryMore Details
    19081568 Degradation of LDLR protein mediated by 'gain of function' PCSK9 mutants in normal and ARH cells.AtherosclerosisMore Details
    19319977 The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene.Human mutationMore Details
    19351729 Genetic and metabolic determinants of plasma PCSK9 levels.The Journal of clinical endocrinology and metabolismMore Details
    19041195 [Familial hypercholesterolemia in Tunisia].Pathologie-biologieMore Details
    19001363 Structural and biochemical characterization of the wild type PCSK9-EGF(AB) complex and natural familial hypercholesterolemia mutants.The Journal of biological chemistryMore Details
    18648394 LDLR promoter variant and exon 14 mutation on the same chromosome are associated with an unusually severe FH phenotype and treatment resistance.European journal of human genetics : EJHGMore Details
    20031607 Longitudinal association of PCSK9 sequence variations with low-density lipoprotein cholesterol levels: the Coronary Artery Risk Development in Young Adults Study.Circulation. Cardiovascular geneticsMore 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
    19191301 Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease.Human mutationMore Details
    19020338 PCSK9: a convertase that coordinates LDL catabolism.Journal of lipid researchMore Details
    19191720 The PCSK9 gene E670G polymorphism affects low-density lipoprotein cholesterol levels but is not a risk factor for coronary artery disease in ethnic Chinese in Taiwan.Clinical chemistry and laboratory medicine : CCLM / FESCCMore Details
    18262190 "Genetic variation at the PCSK9 locus moderately lowers low-density lipoprotein cholesterol levels, but does not significantly lower vascular disease risk in an elderly population."AtherosclerosisMore Details
    18672372 PCSK9 and LDL cholesterol: unravelling the target to design the bullet.Trends in biochemical sciencesMore Details
    18652535 Ethnic differences in the frequency of the cardioprotective C679X PCSK9 mutation in a West African population.Genetic testingMore Details
    18300938 Molecular population genetics of PCSK9: a signature of recent positive selection.Pharmacogenetics and genomicsMore Details
    18498363 PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans.The FEBS journalMore Details
    17765246 Familial hypercholesterolaemia in Portugal.AtherosclerosisMore Details
    18193043 Newly identified loci that influence lipid concentrations and risk of coronary artery disease.Nature geneticsMore Details
    18708425 A PCSK9 variant and familial combined hyperlipidaemia.Journal of medical geneticsMore Details
    18631360 Investigations on the evolutionary conservation of PCSK9 reveal a functionally important protrusion.The FEBS journalMore Details
    18547436 Plasma PCSK9 levels are significantly modified by statins and fibrates in humans.Lipids in health and diseaseMore Details
    17804797 The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain.Proceedings of the National Academy of Sciences of the United States of AmericaMore Details
    17094996 Genetic defects causing familial hypercholesterolaemia: identification of deletions and duplications in the LDL-receptor gene and summary of all mutations found in patients attending the Hammersmith Hospital Lipid Clinic.AtherosclerosisMore Details
    17964958 LDLR and ApoB are major genetic causes of autosomal dominant hypercholesterolemia in a Taiwanese population.Journal of the Formosan Medical Association = Taiwan yi zhiMore Details
    17495605 Unravelling the functional significance of PCSK9.Current opinion in lipidologyMore Details
    17391637 "[After the LDL receptor and apolipoprotein B, autosomal dominant hypercholesterolemia reveals its third protagonist: PCSK9]."Annales d'endocrinologieMore Details
    17599443 Relation of PCSK9 mutations to serum low-density lipoprotein cholesterol in childhood and adulthood (from The Bogalusa Heart Study).The American journal of cardiologyMore Details
    17215125 Molecular biology of PCSK9: its role in LDL metabolism.Trends in biochemical sciencesMore Details
    17550346 The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U.K. men."Clinical science (London, England : 1979)"More Details
    17380167 Mechanisms of disease: genetic causes of familial hypercholesterolemia.Nature clinical practice. Cardiovascular medicineMore Details
    17940607 Proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is a risk factor of large-vessel atherosclerosis stroke.PloS oneMore Details
    17502126 "Of PCSK9, cholesterol homeostasis and parasitic infections: possible survival benefits of loss-of-function PCSK9 genetic polymorphisms."Medical hypothesesMore Details
    16909389 Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote.American journal of human geneticsMore Details
    16987874 Genetic susceptibility to myocardial infarction and coronary artery disease.Human molecular geneticsMore Details
    16415294 A 15-ketosterol is a liver X receptor ligand that suppresses sterol-responsive element binding protein-2 activity.Journal of lipid researchMore Details
    16554528 "Sequence variations in PCSK9, low LDL, and protection against coronary heart disease."The New England journal of medicineMore Details
    16183066 Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia.AtherosclerosisMore Details
    17142622 Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk.Journal of medical geneticsMore Details
    15893176 "A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis."Journal of the American College of CardiologyMore Details
    16224054 Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response."Arteriosclerosis, thrombosis, and vascular biology"More Details
    15321837 Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review.American journal of epidemiologyMore Details
    15523646 LDL-receptor mutations in Europe.Human mutationMore Details
    12730697 Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.Nature geneticsMore Details

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



    PPI interactions

    There were totally 2 unique genes interacted with PCSK9. Show PPI network

    Gene nameInteraction typereference PMIDCHD relation
    PCSK9 in vitro12552133,14622975 CHD related
    LDLR in vitro17435765 CHD related


    Involved FDA drugs

    There was no drug associated with PCSK9