An international study based at the University of Texas (UT) Southwestern Medical Center has revealed a striking genetic-environmental interaction: Obesity significantly amplifies the effects of three gene variants that increase risk of nonalcoholic fatty liver disease (NAFLD) by different metabolic pathways. NAFLD, which in its most serious form can lead to chronic liver disease (cirrhosis) and liver cancer, is a growing problem associated with the obesity epidemic. Despite intense study, the relationship between obesity and NAFLD had remained unresolved. Of the three gene variants, or alleles, examined in this study, the strongest genetic-environmental interactions were found in the PNPLA3 gene variant, the first genetic cause of NAFLD ever identified. That variant was identified in The Dallas Heart Study, a longitudinal, multi-ethnic, population-based study directed by Dr. Helen Hobbs (photo), co-senior author of the Nature Genetics study published online on April 24, 2017. Her scientific partner, Dr. Jonathan Cohen (photo), a Professor of Internal Medicine, is also a senior author. The study’s first author is Dr. Stefan Stender, a postdoctoral researcher from Copenhagen University Hospital working in the Department of Molecular Genetics and the Eugene McDermott Center for Human Growth and Development at UT Southwestern. The Nature Genetics article is titled “Adiposity Amplifies the Genetic Risk of Fatty Liver Disease Conferred by Multiple Loci.” “While all obese individuals who have fatty liver disease would benefit from weight loss, our data suggest that those who have the risk allele in PNPLA3 are likely to benefit more,” said Dr. Hobbs, Director of the McDermott Center, a Howard Hughes Medical Institute (HHMI) Investigator, and a Professor of Internal Medicine and Molecular Genetics.
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