{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:09:31Z","timestamp":1787170171821,"version":"build-2736575974"},"reference-count":9,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Drug-induced QT prolongation (diQTP) can lead to rare, but potentially fatal adverse effects of many medications, yet individual susceptibility varies due to both clinical and genetic factors.\n                      <jats:italic toggle=\"yes\">SDHAF3<\/jats:italic>\n                      p.F53L (rs62624461) is a genetic variant that plays a role in mitochondrial function and was previously associated with diQTP in one small prior study. Therefore, the objective of this retrospective pharmacogenetic study was to evaluate whether\n                      <jats:italic toggle=\"yes\">SDHAF3<\/jats:italic>\n                      p.F53L is associated with clinically significant diQTP. Data were obtained from the Michigan Genomics Initiative, which links genotype information with electronic health records at Michigan Medicine. Adult patients with available genotype and electrocardiogram data who received at least one high-risk QT-prolonging drug between 2001 and 2022 were included. The analysis was limited to 5848 patients of European ancestry, of whom 320 (5.5%) were carriers of the\n                      <jats:italic toggle=\"yes\">SDHAF3<\/jats:italic>\n                      p.F53L variant. QT prolongation was defined as a QTc greater than or equal to 500\u2005ms or an increase greater than 60\u2005ms from baseline during high-risk QT-prolonging drug prescription. Logistic regression under a dominant genetic model assessed associations between variant carrier status and diQTP, with and without propensity score adjustment. Baseline demographics and comorbidities were similar between carriers and noncarriers. No significant association was observed between\n                      <jats:italic toggle=\"yes\">SDHAF3<\/jats:italic>\n                      p.F53L and diQTP [unadjusted odds ratio (OR)\u2005=\u20051.06, 95% confidence interval (CI)\u2005=\u20050.76\u20131.48,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2005=\u20050.742; adjusted OR\u2005=\u20051.05, 95% CI\u2005=\u20050.74\u20131.51,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2005=\u20050.773]. These results suggest that\n                      <jats:italic toggle=\"yes\">SDHAF3<\/jats:italic>\n                      p.F53L does not meaningfully influence diQTP risk in a large, real-world clinical cohort. Future studies should examine this variant across diverse populations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000610","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T20:00:09Z","timestamp":1781553609000},"page":"241-244","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the impact of SDHAF3 p.F53L genetic variant on clinically significant QTc prolongation in patients prescribed high-risk medications: a retrospective pharmacogenetic study"],"prefix":"10.1097","volume":"36","author":[{"given":"Ahmed","family":"Aalibraheem","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I.","family":"Lopez-Medina","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choudhary Anwar A.","family":"Chahal","sequence":"additional","affiliation":[{"name":"Center for Inherited Cardiovascular Diseases, WellSpan Health, Lancaster, Pennsylvania"},{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA"},{"name":"Department of Cardiology, Barts Heart Centre, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine A.","family":"Luzum","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"R1-20260730","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.jacc.2012.03.031","article-title":"Common variation in the NOS1AP gene is associated with drug-induced QT prolongation and ventricular arrhythmia.","volume":"60","author":"Jamshidi","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"R2-20260730","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1161\/CIRCULATIONAHA.116.023980","article-title":"Common genetic variant risk score is associated with drug-induced QT prolongation and torsade de pointes risk: a pilot study.","volume":"135","author":"Strauss","year":"2017","journal-title":"Circulation"},{"key":"R3-20260730","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2217\/pgs-2023-0229","article-title":"Genetic risk factors for drug-induced long QT syndrome: findings from a large 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methods.","volume":"48","author":"Das","year":"2016","journal-title":"Nat Genet"},{"key":"R8-20260730","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jbi.2015.05.003","article-title":"Supporting information retrieval from electronic health records: a report of University of Michigan\u2019s nine-year experience in developing and using the Electronic Medical Record Search Engine (EMERSE).","volume":"55","author":"Hanauer","year":"2015","journal-title":"J Biomed Inform"},{"key":"R9-20260730","doi-asserted-by":"crossref","first-page":"543","DOI":"10.2217\/pgs-2022-0027","article-title":"The genetics of drug-induced QT prolongation: evaluating the evidence for pharmacodynamic variants.","volume":"23","author":"Lopez-Medina","year":"2022","journal-title":"Pharmacogenomics"},{"key":"R10-20260730","doi-asserted-by":"crossref","first-page":"154091","DOI":"10.1016\/j.jelectrocard.2025.154091","article-title":"A comparison of the four most commonly used formulae to adjust the QT-interval for heart rate in 22,000 healthy subjects.","volume":"92","author":"Hoek","year":"2025","journal-title":"J Electrocardiol"}],"container-title":["Pharmacogenetics and Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1097\/FPC.0000000000000610","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:00:42Z","timestamp":1785441642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1097\/FPC.0000000000000610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":9,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1097\/fpc.0000000000000610","relation":{},"ISSN":["1744-6872","1744-6880"],"issn-type":[{"value":"1744-6872","type":"print"},{"value":"1744-6880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]},"assertion":[{"value":"2026-03-19","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-27","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}