{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:04Z","timestamp":1787013904208,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Common genetic variations in the nitric oxide synthase\u20101 adaptor protein (\n                      <jats:italic>NOS1AP<\/jats:italic>\n                      ) gene are associated with QT\u2010interval prolongation. In a previous study, we observed an association between the rs10494366 variant of this gene and an increased QT\u2010interval shortening in digoxin users. As QT\u2010interval shortening is a risk factor for sudden cardiac death (SCD), in this study, we investigated whether the association between digoxin use and risk of SCD differs in participants with different\n                      <jats:italic>NOS1AP<\/jats:italic>\n                      rs10494366 genotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 11\u2009377 individuals from the prospective population\u2010based cohort of the Rotterdam Study. We used Cox proportional hazard regression analysis with digoxin as time\u2010dependent exposure to estimate the associations between current digoxin use and the risk of SCD among different rs10494366 genotype groups in the adjusted models. We also studied whether such an association was dose\u2010dependent, comparing high dosage (\u2265 0.250\u2009mg), moderate dosage (0.125\u2009mg\u2009\u2264\u2009dose&lt; 0.250\u2009mg) and low dosage (&lt; 0.125\u2009mg) digoxin users with non\u2010users.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The median baseline age of the total study population was 62 (interquartile range [IQR] 58\u201371) years. The cumulative incidence of SCD was 4.1% (469 cases), and among them, 74 (15.7%) individuals were current digoxin users at the time of death, during a median follow\u2010up of 11.5 (IQR 6.5\u201317) years. Current digoxin users had an increased risk of SCD (multivariable adjusted model hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 2.38\u20133.98), with no significant differences between the three genotype groups. The adjusted HRs were 4.03 [95% CI: 1.98\u20138.21] in the minor homozygous GG, 3.46 [95% CI: 2.37\u20135.04] in the heterozygous TG and 2.56 [95%CI: 1.70\u20133.86] in the homozygous TT genotype groups. Compared to low\u2010 and moderate\u2010dose, high\u2010dose digoxin users with GG genotype had the highest risk of SCD (HR: 5.61 [95% CI: 1.34\u201323.47]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Current use of digoxin is associated with a significantly increased risk of SCD. The\n                      <jats:italic>NOS1AP<\/jats:italic>\n                      gene rs10494366 variant did not modify the digoxin\u2010associated risk of SCD in a population of European ancestry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.16130","type":"journal-article","created":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:53:02Z","timestamp":1717203182000},"page":"2159-2165","source":"Crossref","is-referenced-by-count":1,"title":["The\n                    <i>NOS1AP<\/i>\n                    gene rs10494366 common genetic variant does not modify the risk of sudden cardiac death in users of digoxin"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3110-9896","authenticated-orcid":false,"given":"Negin","family":"Soroush","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert\u2010Jan","family":"Aarnoudse","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Catharina Hospital  Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Kavousi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A.","family":"Kors","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arfan","family":"Ikram","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno H.","family":"Stricker","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariba","family":"Ahmadizar","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC University Medical Center  Rotterdam The Netherlands"},{"name":"Department of Data Science &amp; Biostatistics, Julius Global Health University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1790"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.364"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.676783"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn341"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2004.11.009"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euw280"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.12.065"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.19\u2010024"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa612"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/HPC.0b013e318221e7dd"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199702203360801"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz395"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2018.09.036"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2510"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2020.05.030"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41397\u2010021\u201000256\u20102"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00145007"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010020\u201000640\u20105"},{"key":"e_1_2_11_20_1","volume-title":"ATC\/DDD index","author":"World Health Organization","year":"2020"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010010\u20109451\u20107"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.2001.2824"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010012\u20109668\u20108"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2014.09.054"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2008.03325.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.08.067"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.117.005485"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2009.03474.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwaa118"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy474"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.03.038"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.70.1.43"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.16130","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T04:07:26Z","timestamp":1724904446000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.16130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,31]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1111\/bcp.16130"],"URL":"https:\/\/doi.org\/10.1111\/bcp.16130","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,31]]}}}