{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:13:00Z","timestamp":1747185180170,"version":"3.40.5"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by inflammation of the intra\u2010 and extrahepatic bile ducts. Pathogenesis of PSC is still enigmatic but is likely to be multifactorial. Recently, we identified an interleukin\u20106 (IL\u20106)\u2010dependent signal transducer and activator of transcription 3 (STAT3) activation in CD4<jats:sup>+<\/jats:sup> TH1 and TH17 cells in PSC. The IL\u20106\/STAT3 pathway was shown to be regulated by protease\u2010activated receptor 1 (PAR1) contributing to inflammation. The role of the <jats:italic>PAR1<\/jats:italic> \u2212506 deletion\/insertion (Del\/Ins) polymorphism in PSC has not yet been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two hundred eighty four PSC patients (200 patients with inflammatory bowel diseases [IBD] and 84 without IBD) and 309 healthy controls were genotyped for <jats:italic>PAR1<\/jats:italic> rs11267092 (\u2212506 Del\/Ins \u221213\u00a0bp). Results were correlated with clinical characteristics and transplant\u2010free survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The frequency of PAR1 \u2013506 Ins allele carriers (Del\/Ins and Ins\/Ins) was significantly higher in PSC patients (57.0%) compared to healthy controls (39.8%). Furthermore, carriers of PAR1 \u2212506 Ins allele were more likely to have PSC than noncarriers (odds ratio 2.01; 95% confidence interval, 1.45\u20132.79). Patients with PSC carrying the PAR1 \u2212506 Ins allele showed significantly higher alanine aminotransferase serum levels (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0357) and a trend toward shorter transplant\u2010free survival time compared to noncarriers (8.9\u00a0\u00b1\u00a06.6\u00a0years vs. 10.5\u00a0\u00b1\u00a07.1\u00a0years; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.076).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study shows that <jats:italic>PAR1<\/jats:italic> \u2212506 Ins is significantly more frequent in people with PSC. As <jats:italic>PAR1<\/jats:italic> \u2212506 Ins allele carriers tended to have a shorter transplant\u2010free survival, <jats:italic>PAR1<\/jats:italic> might play a role in the development and course of PSC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.14035","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T07:05:47Z","timestamp":1711004747000},"page":"942-948","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of <i>PAR1<\/i> \u2212506 deletion\/insertion polymorphism in primary sclerosing cholangitis"],"prefix":"10.1111","volume":"54","author":[{"given":"Bettina","family":"Langhans","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I University Hospital of Bonn  Bonn Germany"},{"name":"German Center for Infection Research (DZIF) Partner Site Cologne\u2010Bonn  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Kalthoff","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital of Bonn  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-5818","authenticated-orcid":false,"given":"Taotao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital of Bonn  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias J.","family":"Weism\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital of Bonn  Bonn Germany"},{"name":"Department of Gastroenterology, Hepatology and Oncology Vivantes Humboldt\u2010Hospital  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrike","family":"Lenzen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3457-0023","authenticated-orcid":false,"given":"Hans Dieter","family":"Nischalke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital of Bonn  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian P.","family":"Strassburg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital of Bonn  Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Lutz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Hospital of Bonn  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