{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T19:43:05Z","timestamp":1781552585016,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/Aims<\/jats:title><jats:p>Longitudinal studies assessing the impact of genetic polymorphisms on outcomes in patients with Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction\u2010Associated Steatotic Liver Disease (MASLD) are scarce. This study aimed to evaluate the effect of PNPLA3 and TM6SF2 risk alleles on hepatic and extrahepatic outcomes in T2DM\u2010MASLD individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients' polymorphisms were analysed as follows: PNPLA3 CC, CG and GG; TM6SF2 CC and CT\u2009+\u2009TT; combined comparing no mutant allele, one allele G or T or \u22652 alleles G or T. Hierarchical models were built to assess associations between polymorphisms and outcomes, independently of confounding factors. Multivariate logistic regression was used for cirrhosis and its complications and extrahepatic cancer, and Cox regression for cardiovascular events (CVEs) and all\u2010cause mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 407 T2DM\u2010MASLD patients (62.1\u2009\u00b1\u200910.5\u2009years, 67.6% women) were followed for 11 (6\u201313) years. Having at least one G or T allele independently increased the risk of cirrhosis in the separate analysis of PNPLA3 and TM6SF2. Combined polymorphism analysis demonstrated an even higher risk of cirrhosis if two or more risk alleles were present (OR 18.48; 95% CI 6.15\u201355.58; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). Regarding cirrhosis complications, the risk was higher in PNPLA3 GG and TM6SF2 CT\u2009+\u2009TT, also with an even higher risk when two or more risk alleles were present in the combined evaluation (OR 27.20; 95% CI 5.26\u2013140.62; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). There were no associations with CVEs or mortality outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In T2DM, PNPLA3 and TM6SF2 polymorphisms, individually and additively, impact MASLD severity, with an increased risk of cirrhosis and its complications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15845","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T09:10:27Z","timestamp":1706692227000},"page":"1042-1050","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Impact of <scp>PNPLA3<\/scp> and <scp>TM6SF2<\/scp> polymorphisms on the prognosis of patients with <scp>MASLD<\/scp> and type 2 diabetes mellitus"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6250-6355","authenticated-orcid":false,"given":"Nat\u00e1lia Coelho","family":"Lavrado","sequence":"first","affiliation":[{"name":"Internal Medicine Post Graduate Program, Medical School Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6318-7077","authenticated-orcid":false,"given":"Gil Fernando","family":"Salles","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4909-0153","authenticated-orcid":false,"given":"Claudia Regina Lopes","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-9132","authenticated-orcid":false,"given":"Paulo Henrique Condeixa","family":"de Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Medicine Department University of Joinville Region \u2013 UNIVILLE  Joinville Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8599-310X","authenticated-orcid":false,"given":"Maria Fernanda Di Guimar\u00e3es Gon\u00e7alves","family":"Melo","sequence":"additional","affiliation":[{"name":"Medical School Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9066-0405","authenticated-orcid":false,"given":"Nathalie Carvalho","family":"Leite","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Clementino Fraga Filho University Hospital Federal University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1355-2368","authenticated-orcid":false,"given":"Cristiane Alves","family":"Villela\u2010Nogueira","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School Federal University of Rio de Janeiro  Rio de Janeiro 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