{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T22:19:30Z","timestamp":1773094770502,"version":"3.50.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Chronic liver disease (CLD) is an extremely common clinical condition accompanied by sustained inflammatory response leading to tissue damage. Transforming growth factor-\u03b21 (TGF-\u03b21) is known as a master immune regulator in CLDs, but the association between TGF-\u03b21 polymorphisms and CLD risk is controversial and inconclusive, and the genetic dominance of CLDs remains unknown. In this study, the relationship between <jats:italic>TGF-\u03b21<\/jats:italic> polymorphisms and CLD susceptibility is systematically analyzed based on 35 eligible studies. Individuals with the <jats:italic>TGF-\u03b21<\/jats:italic>-509 allele (TT or CT) or codon 10 allele (Pro\/Pro) show an increased risk of CLDs. Subgroup analyses indicate <jats:italic>TGF-\u03b21<\/jats:italic>-509C\/T has a significant correlation with cirrhosis and chronic hepatitis C, codon 10 is associated with chronic hepatitis B occurrence, and codon 25 exhibits a relationship with autoimmune hepatitis risk. Missense mutations in G29E, A105S, D191N, and F321L of <jats:italic>TGF-\u03b21<\/jats:italic> are the genetic factors of HCC susceptibility. Furthermore, the <jats:italic>TGF-\u03b21<\/jats:italic> gene expression is significantly elevated in CLD patients, and the <jats:italic>TGF-\u03b21<\/jats:italic> codon 263 is located close to the region where the TGF-\u03b21 dimerization interacts, indicating the <jats:italic>TGF-\u03b21<\/jats:italic> codon 263 variant may affect the secretion of TGF-\u03b21 by altering its dimerization. Together, our findings provide new insights into the immune regulator gene <jats:italic>TGF-\u03b21<\/jats:italic> polymorphisms as susceptibility factors for CLD occurrence and regulators for TGF-\u03b21 expression, which have implications for the regulation of immune factors during CLD development.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1058532","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T04:58:05Z","timestamp":1668574685000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic dominance of transforming growth factor-\u03b21 polymorphisms in chronic liver 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