{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T23:44:02Z","timestamp":1776469442715,"version":"3.51.2"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JGH Open"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Identifying the factors contributing to the progression of metabolic dysfunction\u2010associated steatotic liver disease (MASLD), a lifestyle\u2010related disease, is crucial for preventing future liver\u2010related deaths. This study aimed to epidemiologically investigate factors, including single\u2010nucleotide polymorphisms (SNPs) associated with alanine aminotransferase (ALT) levels &gt;30\u2009U\/L and potential risk factors for liver fibrosis, in a general population cohort of patients with MASLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Among 1059 participants in the health checkup project, 228 who were diagnosed with MASLD were analyzed. Liver fat content and stiffness were measured using FibroScan, and 13 SNPs associated with non\u2010alcoholic fatty liver disease (NAFLD) were measured in addition to other clinical parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the multivariate analysis, male sex, younger age, and high triglyceride levels were significant risk factors for ALT levels &gt;30\u2009U\/L (<jats:italic>P<\/jats:italic>\u2010value\u2009&lt;\u20090.05). Furthermore, among the 13 SNPs measured, only the GG genotypes of patatin\u2010like phospholipase domain\u2010containing 3 gene (PNPLA3) rs738409 and rs2896019 were significant risk factors for ALT levels &gt;30\u2009U\/L (<jats:italic>P<\/jats:italic>\u2010value 0.004 and 0.007). The GG genotypes of PNPLA3 rs738409 and rs2896019 had higher FibroScan\u2010aspartate aminotransferase (FAST) and APRI scores than the CC\u2009+\u2009CG and TT\u2009+\u2009TG genotypes (<jats:italic>P<\/jats:italic>\u2010value\u2009&lt;\u20090.05). In addition, multivariate analysis revealed that the GG genotypes of rs738409 and rs2896019 were significant risk factors independent of cardiovascular metabolic risk for patients with MASLD (<jats:italic>P<\/jats:italic>\u2010value 0.038 and 0.021).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>An individualized treatment approach is warranted for patients with MASLD due to the influence of various factors on its progression, including genetic factors and lifestyle diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgh3.70043","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T06:39:57Z","timestamp":1734676797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An epidemiological study on the factors including genetic polymorphism influencing <scp>ALT<\/scp> &gt;<scp>30\u2009U<\/scp>\/L and liver fibrosis progression in metabolic dysfunction\u2010associated steatotic liver disease among the general population"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-7093","authenticated-orcid":false,"given":"Satoshi","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hematology and Clinical Immunology Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chikara","family":"Iino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hematology and Clinical Immunology Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takafumi","family":"Sasada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hematology and Clinical Immunology Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Go","family":"Soma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hematology and Clinical Immunology Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Furusawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hematology and Clinical Immunology Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenta","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hematology and Clinical Immunology Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Preemptive Medicine Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Mikami","sequence":"additional","affiliation":[{"name":"Department of Preemptive Medicine Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsaku","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Preemptive Medicine Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeyuki","family":"Nakaji","sequence":"additional","affiliation":[{"name":"Department of Preemptive Medicine Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotake","family":"Sakuraba","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hematology and Clinical Immunology Hirosaki University Graduate School of Medicine  Hirosaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(22)00165-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000520"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000000116"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.02.023"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12226"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-020-1165-z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2006.00811.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2008.02.038"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.257"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038322"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-11-172"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1285-z"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0279"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0554"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1294-3"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2014.0019"},{"key":"e_1_2_9_18_1","first-page":"297","article-title":"Association between rs738409 and rs2896019 single\u2010nucleotide polymorphisms of phospholipase domain\u2010containing protein 3 and susceptibility to nonalcoholic fatty liver disease in Greek children and adolescents","volume":"35","author":"Stasinou E","year":"2022","journal-title":"Ann. Gastroenterol."},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001324"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871530320999201126202706"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.4238\/2014.December.4.9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.12.012"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M075028"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2302"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.05.029"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29751"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.766329"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.21814"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185490"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-016-0279-3"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30383-8"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-328689"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-93435-x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-019-1321-x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.09.012"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.155937"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/20503121211002606"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12094"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.2188\/jea.8.203"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.14011"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.68"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9018"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.08.018"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2023.101280"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000323"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2011.10.014"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-0407.2010.00111.x"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.12.022"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1901974116"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22527"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000004569"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24283"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2014.17"},{"key":"e_1_2_9_54_1","first-page":"5212","article-title":"PNPLA3 overexpression results in reduction of proteins predisposing to fibrosis","volume":"25","author":"Pingitore P","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2019.08.002"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-016-1264-3"}],"container-title":["JGH Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgh3.70043","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T04:38:04Z","timestamp":1735533484000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgh3.70043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":55,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/jgh3.70043"],"URL":"https:\/\/doi.org\/10.1002\/jgh3.70043","archive":["Portico"],"relation":{},"ISSN":["2397-9070","2397-9070"],"issn-type":[{"value":"2397-9070","type":"print"},{"value":"2397-9070","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70043"}}