{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T15:24:11Z","timestamp":1764084251399},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T00:00:00Z","timestamp":1412812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T00:00:00Z","timestamp":1412812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lysophosphatidic acid (LPA) mediates cholestatic pruritus. Recently the enzyme PNPLA3, expressed in liver and skin, was demonstrated to metabolise LPA. Here we assess the association of the <jats:italic>PNPLA3<\/jats:italic> variant p.Ile148Met, known to be associated with (non-)alcoholic fatty liver disease (NAFLD) in genome-wide association studies, with cholestatic itch in 187 patients with primary biliary cirrhosis (PBC) and 250 PBC-free controls as well as 201 women with intrahepatic cholestasis of pregnancy (ICP) and 198 female controls without a history of ICP. Our hypothesis was that the intensity of cholestatic itch differs in carriers of distinct <jats:italic>PNPLA3<\/jats:italic> p.Ile148Met genotypes. Patients with PBC carrying the allele p.148Met that confers an increased NAFLD risk reported less itching than carriers of the p.148Ile allele (ANOVA P = 0.048). The <jats:italic>PNPLA3<\/jats:italic> p.148Ile allele increased the odds of requiring plasmapheresis for refractory pruritus (OR = 3.94, 95% CI = 0.91\u201317.00, P = 0.048). In line with these findings, the <jats:italic>PNPLA3<\/jats:italic> p.148Met allele was underrepresented in the ICP cohort (OR = 0.66, 95% CI = 0.47\u20130.92, P = 0.013). Notwithstanding the need for further replication of these findings, we conclude that the <jats:italic>PNPLA3<\/jats:italic> allele p.148Met might confer protection against cholestatic pruritus, possibly due to increased LPA-acyltransferase activity in liver and\/or skin.<\/jats:p>","DOI":"10.1038\/srep06374","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T09:12:09Z","timestamp":1412845929000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Variant adiponutrin confers genetic protection against cholestatic itch"],"prefix":"10.1038","volume":"4","author":[{"given":"Marcin","family":"Krawczyk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Milkiewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanns-Ulrich","family":"Marschall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens","family":"Bartz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Gr\u00fcnhage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Wunsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Milkiewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Lammert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,10,9]]},"reference":[{"key":"BFsrep06374_CR1","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/nrgastro.2013.182","volume":"10","author":"QM Anstee","year":"2013","unstructured":"Anstee, Q. M. & Day, C. P. The genetics of NAFLD. Nat. Rev. Gastroenterol. Hepatol. 10, 645\u2013655 (2013).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"BFsrep06374_CR2","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1038\/ng.257","volume":"40","author":"S Romeo","year":"2008","unstructured":"Romeo, S. et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 40, 1461\u20131465 (2008).","journal-title":"Nat. Genet."},{"key":"BFsrep06374_CR3","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1002\/hep.23823","volume":"52","author":"L Valenti","year":"2010","unstructured":"Valenti, L. et al. I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease. 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