The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease

Luca Miele, G Beale, G Patman, V Nobili, J Leathart, Antonio Grieco, M Abate, Sl Friedman, G Narla, E Bugianesi, Cp Day, Hl Reeves

Risultato della ricerca: Contributo in rivistaArticolo in rivista

152 Citazioni (Scopus)


BACKGROUND & AIMS: Although nonalcoholic fatty liver disease (NAFLD) is increasingly common, only a minority of affected individuals develop fibrotic liver disease. Based on its role in liver growth and repair, we explored whether Kruppel-like factor 6 (KLF6) plays a role in NAFLD progression. METHODS: KLF6 expression in 31 fibrosis scored NAFLD liver biopsy specimens was assessed by real-time polymerase chain reaction. Transfected minigene constructs were used to study the effect of a polymorphism, KLF6-IVS1-27G>A, that promotes KLF6 alternative splicing in vitro. We genotyped KLF6-IVS1-27G>A in 3 groups of patients (UK group 1, n = 306; Italian group 2, n = 109; trio group 3, n = 61 children and parents). RESULTS: KLF6 expression was increased in association with increased steatosis, inflammation, and fibrosis in NAFLD livers. KLF6-IVS1-27G>A promoted alternative splicing of KLF6 and abrogated the up-regulation of both alpha-smooth muscle actin and collagen 1 in LX-2 cells. Group 1 genotyping identified KLF6-IVS1-27G>A in 44 of 306 (14.4%) patients. Notably, KLF6-IVS1-27G>A was associated significantly with milder NAFLD, with only 25% having more advanced fibrosis compared with 45% of wild-type (wt) individuals. This trend was confirmed in group 2. A linear regression analysis including all 415 patients, adjusted for age, sex, body mass index, and blood glucose level, confirmed that presence of the wt KLF6 allele was an independent predictor of fibrotic NAFLD. Furthermore, we have shown preferential transmission of the wt allele to children with fibrotic NAFLD. CONCLUSIONS: We report a functional polymorphism in the KLF6 gene associated with advanced NAFLD and believe further study of KLF6 may enhance our understanding of this disease process.
Lingua originaleEnglish
pagine (da-a)282-291
Numero di pagine10
Stato di pubblicazionePubblicato - 2008


  • KLF6
  • fibrosi
  • steatosi epatica


Entra nei temi di ricerca di 'The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease'. Insieme formano una fingerprint unica.

Cita questo