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NAFLD

PNPLA3 and obesity: a synergistic relationship in NAFLD

NAFLD, the hepatic manifestation of the metabolic syndrome, is a multifactorial condition — environmental factors influence an inherited genetic risk. Stender et al. now describe the additive effect of obesity and NAFLD-associated genetic polymorphisms on steatosis, elevated serum alanine aminotransferase levels and cirrhosis, remarkably illustrating the principle of gene–environment interactions.

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Figure 1: Interaction between PNPLA3 genotype and BMI influences the severity of NAFLD.

References

  1. Anstee, Q. M. & Day, C. P. The genetics of nonalcoholic fatty liver disease: spotlight on PNPLA3 and TM6SF2. Semin. Liver Dis. 35, 270–290 (2015).

    Article  CAS  Google Scholar 

  2. Stender, S. et al. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci. Nat. Genet. 49, 842–847 (2017).

    Article  CAS  Google Scholar 

  3. Liu, Y. L. et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nat. Commun. 5, 4309 (2014).

    Article  CAS  Google Scholar 

  4. Valenti, L. et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 51, 1209–1217 (2010).

    Article  CAS  Google Scholar 

  5. Perry, R. J., Samuel, V. T., Petersen, K. F. & Shulman, G. I. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 510, 84–91 (2014).

    Article  CAS  Google Scholar 

  6. Bruschi, F. V. et al. The PNPLA3 I148M variant modulates the fibrogenic phenotype of human hepatic stellate cells. Hepatology 65, 1875–1890 (2017).

    Article  CAS  Google Scholar 

  7. Lotta, L. A. et al. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat. Genet. 49, 17–26 (2017).

    Article  CAS  Google Scholar 

  8. Mancina, R. M. et al. The MBOAT7-TMC4 variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of European descent. Gastroenterology 150, 1219–1230.e6 (2016).

    Article  CAS  Google Scholar 

  9. Liu, Y. L. et al. Carriage of the PNPLA3 rs738409 C>G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J. Hepatol. 61, 75–81 (2014).

    Article  CAS  Google Scholar 

  10. Shen, J. et al. PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease. J. Gastroenterol. Hepatol. 30, 139–146 (2015).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Q.M.A. is a member of the EPoS (Elucidating Pathways of Steatohepatitis) consortium, which is funded by the Horizon 2020 Framework Program of the European Union under Grant Agreement 634413.

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Correspondence to Quentin M. Anstee.

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Mann, J., Anstee, Q. PNPLA3 and obesity: a synergistic relationship in NAFLD. Nat Rev Gastroenterol Hepatol 14, 506–507 (2017). https://doi.org/10.1038/nrgastro.2017.74

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