The Genetics of progressive NAFLD
Posted 24th April 2019 by Joshua Sewell
Over the last decade, the understanding of genetic factors impacting progressive liver disease has greatly increased. At the 2nd Global NASH Congress, Associate Professor at the University of Milan, Luca Valenti’s research showed the I148M variant of PNPLA3 to be the main common genetic determinant of NAFLD, and how this discovery can be translated into therapeutic approaches.
Multi-ethnic epidemiological studies such as the Dallas Heart Study have provided evidence that genetics play an important role in the predisposition to liver disease.
Subsequent physiological studies have identified the key determinants in the major pathways associated with NAFLD. These concern the uptake of substrates such as glucose, and the activation of glycolysis, lipogenesis, lipid oxidation, lipid secretion, and the remodelling of lipids leading to lipotoxicity and fibrogenesis.
In his presentation, Luca demonstrated how impaired lipid droplet remodelling causes NASH in PNPLA3 I148M carriers, and how the genetic variant is a major predictor of liver fibrosis. He then looked at other genetic variants and the associated pathways relevant to the development of progressive liver disease.
To discover what those other genetic factors are and how they impact the development of NASH, take a look at the slides available below.
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