Genetic variation in the TLL1 gene is not associated with fibrosis in patients with metabolic associated fatty liver disease

PLoS One. 2020 Dec 11;15(12):e0243590. doi: 10.1371/journal.pone.0243590. eCollection 2020.

Abstract

Metabolic associated fatty liver disease (MAFLD) is the most prevalent liver disease in Western nations, with high heritability. A recent study of Japanese patients with the disease suggested that TLL1 rs17047200 is associated with fibrosis; whether a similar association is observed in Caucasian patients with MAFLD is unknown. We investigated the association of the TLL1 rs17047200 polymorphism with liver fibrosis in a cohort of Caucasian patients with MAFLD (n = 728). We also investigated whether TLL1 expression is altered during liver injury in humans, in murine models of fibrosis, and in in-vitro. While TLL1 expression is upregulated in the liver of humans with MAFLD and in mice, the rs17047200 variant was not associated with fibrosis or any other histological features, or with hepatic TLL1 expression. In conclusion, the TLL1 rs17047200 variant is not a risk variant for fibrosis in Caucasian patients with MAFLD. However, TLL1 could be involved in the pathogenesis of liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cohort Studies
  • Fatty Liver / complications
  • Fatty Liver / genetics*
  • Female
  • Genetic Variation
  • Humans
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Tolloid-Like Metalloproteinases / genetics*
  • Up-Regulation

Substances

  • Tolloid-Like Metalloproteinases
  • TLL1 protein, human

Grants and funding

ME and JG are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; National Health and Medical Research Council of Australia (NHMRC) Program Grants (1053206 and 1149976) and Project grants (1107178 and 1108422). EB is supported by Horizon 2020 under grant 634413 for the project EPoS. AB is supported by an Australian Government Research Training Program (RTP) scholarship.