Systems pharmacology of arrhythmias

Science Signaling

Volumn 3, Issue 118, 2010, Pages

  Berger, Seth I ^a   Ma'ayan, Avi ^a   Iyengar, Ravi ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DASATINIB; LAMOTRIGINE; LICARBAZEPINE; LOPERAMIDE; MEMANTINE; MICONAZOLE; ORPHENADRINE; PROMETHAZINE; SEVOFLURANE;

ARTICLE; GENE MUTATION; GENOME; HEART ARRHYTHMIA; HUMAN; LONG QT SYNDROME; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; SINGLE NUCLEOTIDE POLYMORPHISM;

ARRHYTHMIAS, CARDIAC; COMPUTATIONAL BIOLOGY; DISEASE SUSCEPTIBILITY; GENE REGULATORY NETWORKS; GENOME-WIDE ASSOCIATION STUDY; HUMANS; LONG QT SYNDROME; PHARMACEUTICAL PREPARATIONS; POLYMORPHISM, SINGLE NUCLEOTIDE; SYSTEMS BIOLOGY;

EID: 77953720204     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2000723     Document Type: Article

References (79)

1. W. J. Blake, G. Balázsi, M. A. Kohanski, F. J. Isaacs, K. F. Murphy, Y. Kuang, C. R. Cantor, D. R. Walt, J. J. Collins, Phenotypic consequences of promoter-mediated transcriptional noise. Mol. Cell 24, 853-865 (2006).
2. A. Raj, A. van Oudenaarden, Nature, nurture, or chance: Stochastic gene expression and its consequences. Cell 135, 216-226 (2008).
3. S. E. Antonarakis, V. A. McKusick, OMIM passes the 1, 000-disease-gene mark. Nat. Genet. 25, 11 (2000).
4. A. Hamosh, A. F. Scott, J. Amberger, D. Valle, V. A. McKusick, Online Mendelian Inheritance in Man (OMIM). Hum. Mutat. 15, 57-61 (2000).
5. K. I. Goh, M. E. Cusick, D. Valle, B. Childs, M. Vidal, A. L. Barabási, The human disease network. Proc. Natl. Acad. Sci. U. S. A. 104, 8685-8690 (2007).
6. A. L. Barabási, Z. N. Oltvai, Network biology: Understanding the cell's functional organization. Nat. Rev. Genet. 5, 101-113 (2004).
7. I. Feldman, A. Rzhetsky, D. Vitkup, Network properties of genes harboring inherited disease mutations. Proc. Natl. Acad. Sci. U. S. A. 105, 4323-4328 (2008).
8. R. Albert, Scale-free networks in cell biology. J. Cell Sci. 118, 4947-4957 (2005).
9. U. Alon, Network motifs: Theory and experimental approaches. Nat. Rev. Genet. 8, 450-461 (2007).
10. V. Spirin, L. A. Mirny, Protein complexes and functional modules in molecular networks. Proc. Natl. Acad. Sci. U. S. A. 100, 12123-12128 (2003).
11. J. Aerssens, A. D. Paulussen, Pharmacogenomics and acquired long QT syndrome. Pharmacogenomics 6, 259-270 (2005).
12. K. Miller-Jensen, K. A. Janes, J. S. Brugge, D. A. Lauffenburger, Common effector processing mediates cell-specific responses to stimuli. Nature 448, 604-608 (2007).
13. J. D. Jordan, E. M. Landau, R. Iyengar, Signaling networks: The origins of cellular multitasking. Cell 103, 193-200 (2000).
14. D. M. Roden, Clinical practice. Long-QT syndrome. N. Engl. J. Med. 358, 169-176 (2008).
15. D. M. Roden, Human genomics and its impact on arrhythmias. Trends Cardiovasc. Med. 14, 112-116 (2004).
16. D. M. Roden, Long QT syndrome: Reduced repolarization reserve and the genetic link. J. Intern. Med. 259, 59-69 (2006).
17. D. Wang, V. V. Patel, E. Ricciotti, R. Zhou, M. D. Levin, E. Gao, Z. Yu, V. A. Ferrari, M. M. Lu, J. Xu, H. Zhang, Y. Hui, Y. Cheng, N. Petrenko, Y. Yu, G. A. FitzGerald, Cardiomyocyte cyclooxygenase-2 influences cardiac rhythm and function. Proc. Natl. Acad. Sci. U. S. A. 106, 7548-7552 (2009).
18. M. J. Kilborn, R. L. Woosley, Registry for torsades de pointes with drug treatment exists. BMJ 322, 672-673 (2001).
19. D. Layton, C. Key, S. A. Shakir, Prolongation of the QT interval and cardiac arrhythmias associated with cisapride: Limitations of the pharmacoepidemiological studies conducted and proposals for the future. Pharmacoepidemiol. Drug Saf. 12, 31-40 (2003).
20. M. A. González, K. S. Estes, Pharmacokinetic overview of oral second-generation H1 antihistamines. Int. J. Clin. Pharmacol. Ther. 36, 292-300 (1998).
21. P. Hoffmann, B. Warner, Are hERG channel inhibition and QT interval prolongation all there is in drug-induced torsadogenesis? A review of emerging trends. J. Pharmacol. Toxicol. Methods 53, 87-105 (2006).
22. S. I. Berger, J. M. Posner, A. Ma'ayan, Genes2Networks: Connecting lists of gene symbols using mammalian protein interactions databases. BMC Bioinformatics 8, 372 (2007).
23. L. M. Camargo, V. Collura, J. C. Rain, K. Mizuguchi, H. Hermjakob, S. Kerrien, T. P. Bonnert, P. J. Whiting, N. J. Brandon, Disrupted in Schizophrenia 1 Interactome: Evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Mol. Psychiatry 12, 74-86 (2007).
24. D. R. Hyduke, L. R. Jarboe, L. M. Tran, K. J. Chou, J. C. Liao, Integrated network analysis identifies nitric oxide response networks and dihydroxyacid dehydratase as a crucial target in Escherichia coli. Proc. Natl. Acad. Sci. U. S. A. 104, 8484-8489 (2007).
25. J. Lim, T. Hao, C. Shaw, A. J. Patel, G. Szabó, J. F. Rual, C. J. Fisk, N. Li, A. Smolyar, D. E. Hill, A. L. Barabási, M. Vidal, H. Y. Zoghbi, A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 125, 801-814 (2006).
26. J. Chen, B. J. Aronow, A. G. Jegga, Disease candidate gene identification and prioritization using protein interaction networks. BMC Bioinformatics 10, 73 (2009).
27. J. Y. Chen, C. Shen, A. Y. Sivachenko, Mining Alzheimer disease relevant proteins from integrated protein interactome data. Pac. Symp. Biocomput. 367-378 (2006).
28. C. I. Petersen, T. R. McFarland, S. Z. Stepanovic, P. Yang, D. J. Reiner, K. Hayashi, A. L. George, D. M. Roden, J. H. Thomas, J. R. Balser, In vivo identification of genes that modify ether-a-go-go-related gene activity in Caenorhabditis elegans may also affect human cardiac arrhythmia. Proc. Natl. Acad. Sci. U. S. A. 101, 11773-11778 (2004).
29. S. Köhler, S. Bauer, D. Horn, P. N. Robinson, Walking the interactome for prioritization of candidate disease genes. Am. J. Hum. Genet. 82, 949-958 (2008).
30. J. G. Kemeny, J. L. Snell, Finite Markov Chains (Springer-Verlag, New York, 1983).
31. J. Freudenberg, P. Propping, A similarity-based method for genome-wide prediction of disease-relevant human genes. Bioinformatics 18 (Suppl. 2), S110-S115 (2002).
32. L. Chen, M. L. Marquardt, D. J. Tester, K. J. Sampson, M. J. Ackerman, R. S. Kass, Mutation of an A-kinase-anchoring protein causes long-QT syndrome. Proc. Natl. Acad. Sci. U. S. A. 104, 20990-20995 (2007).
33. K. Ueda, C. Valdivia, A. Medeiros-Domingo, D. J. Tester, M. Vatta, G. Farrugia, M. J. Ackerman, J. C. Makielski, Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc. Natl. Acad. Sci. U. S. A. 105, 9355-9360 (2008).
34. D. E. Arking, A. Pfeufer, W. Post, W. H. Kao, C. Newton-Cheh, M. Ikeda, K. West, C. Kashuk, M. Akyol, S. Perz, S. Jalilzadeh, T. Illig, C. Gieger, C. Y. Guo, M. G. Larson, H. E. Wichmann, E. Marban, C. J. O'Donnell, J. N. Hirschhorn, S. Kääb, P. M. Spooner, T. Meitinger, A. Chakravarti, A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat. Genet. 38, 644-651 (2006).
35. N. H. Nielsen, B. G. Winkel, J. K. Kanters, N. Schmitt, J. Hofman-Bang, H. S. Jensen, B. H. Bentzen, B. Sigurd, L. A. Larsen, P. S. Andersen, S. Haunsø, K. Kjeldsen, M. Grunnet, M. Christiansen, S. P. Olesen, Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients. Biochem. Biophys. Res. Commun. 354, 776-782 (2007).
36. The Gene Ontology Consortium. The Gene Ontology project in 2008. Nucleic Acids Res. 36, D440-D444 (2008).
37. A. Hamosh, A. F. Scott, J. S. Amberger, C. A. Bocchini, V. A. McKusick, Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 33, D514-D517 (2005).
38. P. L. Hedley, P. Jørgensen, S. Schlamowitz, R. Wangari, J. Moolman-Smook, P. A. Brink, J. K. Kanters, V. A. Corfield, M. Christiansen, The genetic basis of long QT and short QT syndromes: A mutation update. Hum. Mutat. 30, 1486-1511 (2009).
39. U. Patel, B. B. Pavri, Short QT syndrome: A review. Cardiol. Rev. 17, 300-303 (2009).
40. R. Schimpf, C. Veltmann, C. Wolpert, M. Borggrefe, Channelopathies: Brugada syndrome, long QT syndrome, short QT syndrome, and CPVT. Herz 34, 281-288 (2009).
41. S. Zellerhoff, R. Pistulli, G. Mönnig, M. Hinterseer, B. M. Beckmann, J. Köbe, G. Steinbeck, S. Kääb, W. Haverkamp, L. Fabritz, R. Gradaus, G. Breithardt, E. Schulze-Bahr, D. Bocker, P. Kirchhof, Atrial arrhythmias in long-QT syndrome under daily life conditions: A nested case control study. J. Cardiovasc. Electrophysiol. 20, 401-407 (2009).
42. C. F. Barrett, R. W. Tsien, The Timothy syndrome mutation differentially affects voltageand calcium-dependent inactivation of CaV1.2 L-type calcium channels. Proc. Natl. Acad. Sci. U. S. A. 105, 2157-2162 (2008).
43. R. A. Weir, C. J. Petrie, V. Murday, I. N. Findlay, Andersen-Tawil syndrome. Int. J. Cardiol., in press.
44. K. J. Bär, M. Koschke, M. K. Boettger, S. Berger, A. Kabisch, H. Sauer, A. Voss, V. K. Yeragani, Acute psychosis leads to increased QT variability in patients suffering from schizophrenia. Schizophr. Res. 95, 115-123 (2007).
45. A. H. Glassman, J. T. Bigger Jr., Antipsychotic drugs: Prolonged QTc interval, torsade de pointes, and sudden death. Am. J. Psychiatry 158, 1774-1782 (2001).
46. V. L. Vetter, J. Elia, C. Erickson, S. Berger, N. Blum, K. Uzark, C. L. Webb, Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: A scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation 117, 2407-2423 (2008).
47. J. N. Johnson, N. Hofman, C. M. Haglund, G. D. Cascino, A. A. Wilde, M. J. Ackerman, Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy. Neurology 72, 224-231 (2009).
48. P. Minoretti, P. Politi, V. Martinelli, E. Emanuele, M. Bertona, C. Falcone, D. Geroldi, QT interval duration in apparently healthy men is associated with depression-related personality trait neuroticism. J. Psychosom. Res. 61, 19-23 (2006).
49. C. Li, D. Hu, L. Shang, S. Ma, W. Liu, Y. Li, Z. Ma, C. Tang, Y. Mei, L. Wang, Surgical left cardiac sympathetic denervation for long QT syndrome: Effects on QT interval and heart rate. Heart Vessels 20, 137-141 (2005). (Pubitemid 41031010)
50. A. S. Shamsuzzaman, M. J. Ackerman, T. Kara, P. Lanfranchi, V. K. Somers, Sympathetic nerve activity in the congenital long-QT syndrome. Circulation 107, 1844-1847 (2003).
51. C. Omichi, Y. Momose, S. Kitahara, Congenital long QT syndrome presenting with a history of epilepsy: Misdiagnosis or relationship between channelopathies of the heart and brain? Epilepsia 51, 289-292 (2010).
52. A. Pfeufer, S. Sanna, D. E. Arking, M. Müller, V. Gateva, C. Fuchsberger, G. B. Ehret, M. Orrú, C. Pattaro, A. Köttgen, S. Perz, G. Usala, M. Barbalic, M. Li, B. Pütz, A. Scuteri, R. J. Prineas, M. F. Sinner, C. Gieger, S. S. Najjar, W. H. Kao, T. W. Muhleisen, M. Dei, C. Happle, S. Möhlenkamp, L. Crisponi, R. Erbel, K. H. Jöckel, S. Naitza, G. Steinbeck, F. Marroni, A. A. Hicks, E. Lakatta, B. Müller-Myhsok, P. P. Pramstaller, H. E. Wichmann, D. Schlessinger, E. Boerwinkle, T. Meitinger, M. Uda, J. Coresh, S. Kääb, G. R. Abecasis, A. Chakravarti, Common variants at ten loci modulate the QT interval duration in the QTSCD study. Nat. Genet. 41, 407-414 (2009).
53. C. Newton-Cheh, M. Eijgelsheim, K. M. Rice, P. I. de Bakker, X. Yin, K. Estrada, J. C. Bis, K. Marciante, F. Rivadeneira, P. A. Noseworthy, N. Sotoodehnia, N. L. Smith, J. I. Rotter, J. A. Kors, J. C. Witteman, A. Hofman, S. R. Heckbert, C. J. O'Donnell, A. G. Uitterlinden, B. M. Psaty, T. Lumley, M. G. Larson, B. H. Stricker, Common variants at ten loci influence QT interval duration in the QTGEN Study. Nat. Genet. 41, 399-406 (2009).
54. D. J. Milan, A. M. Kim, J. R. Winterfield, I. L. Jones, A. Pfeufer, S. Sanna, D. E. Arking, A. H. Amsterdam, K. M. Sabeh, J. D. Mably, D. S. Rosenbaum, R. T. Peterson, A. Chakravarti, S. Kääb, D. M. Roden, C. A. MacRae, Drug-sensitized zebrafish screen identifies multiple genes, including GINS3, as regulators of myocardial repolarization. Circulation 120, 553-559 (2009).
55. E. Poluzzi, E. Raschi, U. Moretti, F. De Ponti, Drug-induced torsades de pointes: Data mining of the public version of the FDA Adverse Event Reporting System (AERS). Pharmacoepidemiol. Drug Saf. 18, 512-518 (2009).
56. D. S. Wishart, C. Knox, A. C. Guo, D. Cheng, S. Shrivastava, D. Tzur, B. Gautam, M. Hassanali, DrugBank: A knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 36, D901-D906 (2008).
57. D. S. Wishart, C. Knox, A. C. Guo, S. Shrivastava, M. Hassanali, P. Stothard, Z. Chang, J. Woolsey, DrugBank: A comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 34, D668-D672 (2006).
58. R. L. Woosley, Drugs That Prolong the QT Interval and/or Induce Torsades de Pointes. (Arizona CERT, Tucson, AZ, 2007), http://qtdrugs.org/.
59. 2 interactions. Channels (Austin) 4, 3-11 (2010).
60. J. Zhang, P. L. Yang, N. S. Gray, Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer 9, 28-39 (2009).
61. D. Y. Zhang, Y. Wang, C. P. Lau, H. F. Tse, G. R. Li, Both EGFR kinase and Src-related tyrosine kinases regulate human ether-à-go-go-related gene potassium channels. Cell. Signal. 20, 1815-1821 (2008).
62. M. J. Keiser, V. Setola, J. J. Irwin, C. Laggner, A. I. Abbas, S. J. Hufeisen, N. H. Jensen, M. B. Kuijer, R. C. Matos, T. B. Tran, R. Whaley, R. A. Glennon, J. Hert, K. L. Thomas, D. D. Edwards, B. K. Shoichet, B. L. Roth, Predicting new molecular targets for known drugs. Nature 462, 175-181 (2009).
63. R. Platt, M. Wilson, K. A. Chan, J. S. Benner, J. Marchibroda, M. McClellan, The new Sentinel Network-Improving the evidence of medical-product safety. N. Engl. J. Med. 361, 645-647 (2009).
64. H. Yildirim, T. Adanir, A. Atay, K. Katircioǧlu, S. Savaci, The effects of sevoflurane, isoflurane and desflurane onQTinterval of the ECG. Eur. J. Anaesthesiol. 21, 566-570 (2004).
65. L. Fauchier, D. Babuty, P. Poret, M. L. Autret, P. Cosnay, J. P. Fauchier, Effect of verapamil on QT interval dynamicity. Am. J. Cardiol. 83, 807-808, A10-A11 (1999).
66. T. Beuming, L. Skrabanek, M. Y. Niv, P. Mukherjee, H. Weinstein, PDZBase: A protein-protein interaction database for PDZ-domains. Bioinformatics 21, 827-828 (2005).
67. B. J. Breitkreutz, C. Stark, T. Reguly, L. Boucher, A. Breitkreutz, M. Livstone, R. Oughtred, D. H. Lackner, J. Bähler, V. Wood, K. Dolinski, M. Tyers, The BioGRID Interaction Database: 2008 update. Nucleic Acids Res. 36, D637-D640 (2008).
68. A. Chatr-aryamontri, A. Ceol, L. M. Palazzi, G. Nardelli, M. V. Schneider, L. Castagnoli, G. Cesareni, MINT: The Molecular INTeraction database. Nucleic Acids Res. 35, D572-D574 (2007).
69. F. Diella, C. M. Gould, C. Chica, A. Via, T. J. Gibson, Phospho. ELM: A database of phosphorylation sites-Update 2008. Nucleic Acids Res. 36, D240-D244 (2008).
70. S. Kerrien, Y. Alam-Faruque, B. Aranda, I. Bancarz, A. Bridge, C. Derow, E. Dimmer, M. Feuermann, A. Friedrichsen, R. Huntley, C. Kohler, J. Khadake, C. Leroy, A. Liban, C. Lieftink, L. Montecchi-Palazzi, S. Orchard, J. Risse, K. Robbe, B. Roechert, D. Thorneycroft, Y. Zhang, R. Apweiler, H. Hermjakob, IntAct-Open source resource for molecular interaction data. Nucleic Acids Res. 35, D561-D565 (2007).
71. D. Maglott, J. Ostell, K. D. Pruitt, T. Tatusova, Entrez Gene: Gene-centered information at NCBI. Nucleic Acids Res. 35, D26-D31 (2007).
72. H. W. Mewes, S. Dietmann, D. Frishman, R. Gregory, G. Mannhaupt, K. F. Mayer, M. Münsterkötter, A. Ruepp, M. Spannagl, V. Stumpflen, T. Rattei, MIPS: Analysis and annotation of genome information in 2007. Nucleic Acids Res. 36, D196-D201 (2008).
73. G. R. Mishra, M. Suresh, K. Kumaran, N. Kannabiran, S. Suresh, P. Bala, K. Shivakumar, N. Anuradha, R. Reddy, T. M. Raghavan, S. Menon, G. Hanumanthu, M. Gupta, S. Upendran, S. Gupta, M. Mahesh, B. Jacob, P. Mathew, P. Chatterjee, K. S. Arun, S. Sharma, K. N. Chandrika, N. Deshpande, K. Palvankar, R. Raghavnath, R. Krishnakanth, H. Karathia, B. Rekha, R. Nayak, G. Vishnupriya, H. G. Kumar, M. Nagini, G. S. Kumar, R. Jose, P. Deepthi, S. S. Mohan, T. K. Gandhi, H. C. Harsha, K. S. Deshpande, M. Sarker, T. S. Prasad, A. Pandey, Human protein reference database-2006 update. Nucleic Acids Res. 34, D411-D414 (2006).
74. L. Salwinski, C. S. Miller, A. J. Smith, F. K. Pettit, J. U. Bowie, D. Eisenberg, The Database of Interacting Proteins: 2004 update. Nucleic Acids Res. 32, D449-D451 (2004).
75. I. Vastrik, P. D'Eustachio, E. Schmidt, G. Joshi-Tope, G. Gopinath, D. Croft, B. de Bono, M. Gillespie, B. Jassal, S. Lewis, L. Matthews, G. Wu, E. Birney, L. Stein, Reactome: A knowledge base of biologic pathways and processes. Genome Biol. 8, R39 (2007).
76. C. J. Bult, J. T. Eppig, J. A. Kadin, J. E. Richardson, J. A. Blake, Mouse Genome Database Group, The Mouse Genome Database (MGD): Mouse biology and model systems. Nucleic Acids Res. 36, D724-D728 (2008).
77. A. Ma'ayan, S. L. Jenkins, J. Goldfarb, R. Iyengar, Network analysis of FDA approved drugs and their targets. Mt. Sinai J. Med. 74, 27-32 (2007).
78. R. L. Woosley, Discovering adverse reactions: Why does it take so long? Clin. Pharmacol. Ther. 76, 287-289 (2004).
79. Acknowledgments: We thank D. Roden for providing the original LQTS seed gene list that started this project and for additional helpful conversations. We also thank A. Chakravarti and the QTSCD Consortium for providing the QTSCD GWAS data set. Funding: This work was supported by the NIH (grant DK038761) and the Systems Biology Center New York (grant P50GM07558). S. I. B. was supported by Pharmacological Sciences Training Grant GM062754. R. I. and A. M. were supported by a Clinical and Translational Science Award (UL1RR029887) from National Center for Research Resources. Author contributions: S. I. B., A. M., and R. I. developed the initial ideas and hypotheses for the analyses. S. I. B. and A. M. developed the database and networks for the analyses. S. I. B. conducted all of the computational analyses. All authors analyzed the results and participated in writing the paper. Competing interests: The authors have no competing interests.