{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:07:42Z","timestamp":1785413262081,"version":"3.56.0"},"reference-count":31,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Metabolic Syndrome and Related Disorders"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of global liver morbidity. Genetic variants, particularly in the patatin-like phospholipase domain-containing 3 (\n                    <jats:italic toggle=\"yes\">PNPLA3<\/jats:italic>\n                    ) gene, are critical determinants of metabolic traits and disease progression. This study presents the first meta-analysis to clarify the association between the\n                    <jats:italic toggle=\"yes\">PNPLA3<\/jats:italic>\n                    rs2896019 polymorphism and MASLD susceptibility and severity. We systematically searched PubMed, Embase, Web of Science, and Google Scholar for relevant articles published up to February 12, 2026. Data were extracted, and summary estimates of the association between\n                    <jats:italic toggle=\"yes\">PNPLA3<\/jats:italic>\n                    rs2896019 and MASLD were assessed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to measure the effect. Ten eligible case\u2013control cohorts involving 15,028 participants (3118 cases and 11,910 controls) were included. Our results demonstrated that the G allele is significantly associated with a 51% increased risk of MASLD (OR: 1.5, CI: 1.23\u20131.85,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.0001). A clear gene-dose effect was observed, with risks escalating in the homozygous model (OR: 2.32, 95% CI: 1.53\u20133.53,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.0001). Subgroup analysis revealed that diagnostic modality was the primary source of heterogeneity, whereby restricting the analysis to biopsy-proven cohorts eliminated heterogeneity (\n                    <jats:italic toggle=\"yes\">\n                      I\n                      <jats:sup>2<\/jats:sup>\n                      =\n                    <\/jats:italic>\n                    0%) and strengthened the association (OR = 1.91). Furthermore, the G allele significantly increased the risk of severe MASLD\/MASH (OR = 2.06) compared to mild steatosis (OR = 1.40). In conclusion, the\n                    <jats:italic toggle=\"yes\">PNPLA3<\/jats:italic>\n                    rs2896019 G allele is a robust, dose-dependent risk factor for both the development and severe progression of MASLD.\n                  <\/jats:p>","DOI":"10.1177\/15578518261443934","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:46:01Z","timestamp":1776426361000},"page":"285-293","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Patatin-Like Phospholipase Domain-Containing Protein 3 rs2896019 and MASLD Susceptibility and Severity in Adults: A Systematic Review and Meta-Analysis of Case\u2013Control Studies"],"prefix":"10.1177","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5329-9868","authenticated-orcid":false,"given":"Wei-Yue","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosmawati","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuh-Fen","family":"Pung","sequence":"additional","affiliation":[{"name":"Division of Biomedical Science, School of Pharmacy, University of Nottingham Malaysia, Semenyih, Malaysia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hak-Keith","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Xiang","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamsul Mohd","family":"Zain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.06.003"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/edm2.70132"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13685"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12982-025-00496-8"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metop.2025.100424"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2024.0431"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.02.007"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27041933"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2016.0109"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01497-6"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.20517\/jtgg.2024.70"},{"issue":"3","key":"e_1_3_2_13_1","first-page":"297","article-title":"Association between rs738409 and rs2896019 single-nucleotide polymorphisms of phospholipase domain-containing protein 3 and susceptibility to nonalcoholic fatty liver disease in Greek children and adolescents","volume":"35","author":"Stasinou E","year":"2022","unstructured":"12.Stasinou E, , Argyraki M, , Sotiriadou F, et al. Association between rs738409 and rs2896019 single-nucleotide polymorphisms of phospholipase domain-containing protein 3 and susceptibility to nonalcoholic fatty liver disease in Greek children and adolescents. Ann Gastroenterol 2022;35(3):297\u2013306; doi: 10.20524\/aog.2022.0706","journal-title":"Ann Gastroenterol"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16081239"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27010473"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.257"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/377138"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-012-1141-y"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1294-3"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000004569"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185490"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2014.0019"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32788-x"},{"key":"e_1_3_2_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb47080605"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2024.0481"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv402"},{"key":"e_1_3_2_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgh3.70043"},{"key":"e_1_3_2_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2018.01.001"},{"key":"e_1_3_2_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-0329"},{"key":"e_1_3_2_30_1","doi-asserted-by":"publisher","DOI":"10.1086\/518313"},{"key":"e_1_3_2_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1423-0127-16-73"},{"key":"e_1_3_2_32_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i40.6053"}],"container-title":["Metabolic Syndrome and Related Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15578518261443934","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15578518261443934","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15578518261443934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:29Z","timestamp":1785411389000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15578518261443934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,9,1]]}},"alternative-id":["10.1177\/15578518261443934"],"URL":"https:\/\/doi.org\/10.1177\/15578518261443934","relation":{},"ISSN":["1540-4196","1557-8518"],"issn-type":[{"value":"1540-4196","type":"print"},{"value":"1557-8518","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]}}}