Genetic dominance of transforming growth factor-β1 polymorphisms in chronic liver disease.

Chronic liver disease (CLD) is an extremely common clinical condition accompanied by sustained inflammatory response leading to tissue damage. Transforming growth factor-β1 (TGF-β1) is known as a master immune regulator in CLDs, but the association between TGF-β1 polymorphisms and CLD risk is controversial and inconclusive, and the genetic dominance of CLDs remains unknown. In this study, the relationship between polymorphisms and CLD susceptibility is systematically analyzed based on 35 eligible studies. Individuals with the -509 allele (TT or CT) or codon 10 allele (Pro/Pro) show an increased risk of CLDs. Subgroup analyses indicate -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 are the genetic factors of HCC susceptibility. Furthermore, the gene expression is significantly elevated in CLD patients, and the codon 263 is located close to the region where the TGF-β1 dimerization interacts, indicating the codon 263 variant may affect the secretion of TGF-β1 by altering its dimerization. Together, our findings provide new insights into the immune regulator gene polymorphisms as susceptibility factors for CLD occurrence and regulators for TGF-β1 expression, which have implications for the regulation of immune factors during CLD development.