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A four\u2010phase study was conducted with a large cohort of acute pancreatitis (AP) patients (<jats:italic>n<\/jats:italic>\u2009=\u2009600). In the first phase, whole\u2010exome sequencing identified a specific exonic variant (rs1326680184) in the human Fc gamma binding protein (<jats:italic>FCGBP<\/jats:italic>) gene consistently associated with SIH. The second phase employed serum ELISA tests, revealing that this variant altered FCGBP protein levels, increasing susceptibility to SIH. In the third phase, functional validation was performed through: (i) in vivo experiments using a <jats:italic>Fcgbp<\/jats:italic>\u2010knockdown mouse model demonstrated that reduced <jats:italic>Fcgbp<\/jats:italic> expression exacerbated AP severity and increased the risk of hemorrhage; and (ii) in vitro experiments with <jats:italic>FCGBP<\/jats:italic>\u2010knockdown in human vascular fibroblasts showed that decreased <jats:italic>FCGBP<\/jats:italic> expression destabilized the vascular wall, leading to vascular injury in SAP. Finally, the fourth phase compared clinical characteristics of <jats:italic>FCGBP<\/jats:italic> rs1326680184 carriers and non\u2010carriers, finding that carriers exhibited higher risks of severe complications, worse AP prognosis, and demonstrated enhanced diagnostic utility as a predictive indicator. These findings provide critical insights into the genetic basis of SIH in SAP, paving the way for precision therapies and effective prognostic tools to improve AP management and early intervention.<\/jats:p>","DOI":"10.1002\/imo2.52","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T01:39:49Z","timestamp":1736473189000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whole exome sequencing reveals an <i>FCGBP<\/i> variant associated with spontaneous intraabdominal hemorrhage in severe acute pancreatitis"],"prefix":"10.1002","volume":"2","author":[{"given":"Qiu\u2010Yi","family":"Tang","sequence":"first","affiliation":[{"name":"School of Medicine Southeast University Nanjing China"},{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"},{"name":"Department of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue\u2010Peng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"},{"name":"Department of Emergency Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Medicine Southeast University Nanjing China"},{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing\u2010Zhu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai\u2010Bin","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bai\u2010Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi\u2010Hui","family":"Tong","sequence":"additional","affiliation":[{"name":"School of Medicine Southeast University Nanjing China"},{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Xiu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-5087","authenticated-orcid":false,"given":"Evan Yi\u2010Wen","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Epidemiology &amp; 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