{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:25:37Z","timestamp":1792092337946,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,3,13]],"date-time":"2009-03-13T00:00:00Z","timestamp":1236902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p> <jats:italic>Background:<\/jats:italic> Type\u20101 long\u2010QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage\u2010gated potassium channel family are associated with an increased risk of cardiac events.<\/jats:p><jats:p> <jats:italic>Methods and Results:<\/jats:italic> The study population involved 492 LQT1 patients with 54 missense mutations in the transmembrane region of the KCNQ1 channel. The amino acid sequences of the transmembrane region of 38 human voltage\u2010gated potassium channels were aligned. An adjusted Shannon entropy score for each amino acid residue was calculated ranging from 0 (no conservation) to 1.0 (full conservation). Cox analysis was used to identify independent factors associated with the first cardiac event (syncope, aborted cardiac arrest, or death). Patients were subcategorized into tertiles by their adjusted Shannon entropy scores. The lowest tertile (score 0\u20130.469; n = 146) was used as a reference group; patients with intermediate tertile scores (0.470\u20130.665; n = 150) had no increased risk of cardiac events (HR = 1.19, P = 0.42) or aborted cardiac arrest\/sudden cardiac death (HR = 1.58, P = 0.26), and those with the highest tertile scores (&gt;0.665; n = 196) showed significantly increased risk of cardiac events (HR = 3.32, P &lt;0.001) and aborted cardiac arrest\/sudden cardiac death (HR = 2.62, P = 0.04). The increased risk in patients with the highest conservation scores was independent of QTc, gender, age, and beta\u2010blocker therapy.<\/jats:p><jats:p> <jats:italic>Conclusions:<\/jats:italic> Mutations in highly conserved amino acid residues in the KCNQ1 gene are associated with a significant risk of cardiac events independent of QTc, gender, and beta\u2010blocker therapy.<\/jats:p>","DOI":"10.1111\/j.1540-8167.2009.01455.x","type":"journal-article","created":{"date-parts":[[2009,3,13]],"date-time":"2009-03-13T16:42:06Z","timestamp":1236962526000},"page":"859-865","source":"Crossref","is-referenced-by-count":30,"title":["Mutations in Conserved Amino Acids in the KCNQ1 Channel and Risk of Cardiac Events in Type\u20101 Long\u2010QT Syndrome"],"prefix":"10.1111","volume":"20","author":[{"given":"CHRISTIAN","family":"JONS","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ARTHUR J.","family":"MOSS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"COELI M.","family":"LOPES","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SCOTT","family":"MCNITT","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WOJCIECH","family":"ZAREBA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ILAN","family":"GOLDENBERG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MING","family":"QI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ARTHUR A. M.","family":"WILDE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WATARU","family":"SHIMIZU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JORGEN K.","family":"KANTERS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JEFFREY A.","family":"TOWBIN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MICHAEL J.","family":"ACKERMAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JENNIFER L.","family":"ROBINSON","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,7,28]]},"reference":[{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2000.tb00035.x"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-17"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.148254"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116269"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi701597s"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00031.2005"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.16.2041"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.665406"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.11.1341"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1540-8167.2003.02545.x"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022147"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.296.10.1249"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340110408"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10146"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1538-7305.1948.tb01338.x"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm270"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg500"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1989.10478874"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2000.1323"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.02.010"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.145813"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2005.01.020"},{"key":"e_1_2_10_24_2","doi-asserted-by":"crossref","DOI":"10.2202\/1544-6115.1074","article-title":"Statistical methods for identifying conserved residues in multiple sequence alignment","volume":"3","author":"Ahola V","year":"2004","journal-title":"Stat Appl Genet Mol Biol"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-381"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm626"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4540"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl495"}],"container-title":["Journal of Cardiovascular Electrophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1540-8167.2009.01455.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1540-8167.2009.01455.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T22:27:34Z","timestamp":1696976854000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1540-8167.2009.01455.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7,28]]},"references-count":27,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2009,8]]}},"alternative-id":["10.1111\/j.1540-8167.2009.01455.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1540-8167.2009.01455.x","archive":["Portico"],"relation":{},"ISSN":["1045-3873","1540-8167"],"issn-type":[{"value":"1045-3873","type":"print"},{"value":"1540-8167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7,28]]}}}