Diabetic Status Modifies Impact of an NAFLD-Associated SNP

Non-alcoholic steatohepatitis (NASH) is a common disease that affect nearly billion people globally and so early identification of susceptible individuals is critical for precision hepatology. In this issue, Takebe et al. use human liver organoids and perform en masse population-based phenotypic analysis under insulin insensitive conditions to investigate key NASH-genetic factors. In the image, multiple flying butterflies with liver-like wings suggest liver organoids at “population” scale. Some butterflies are caught by the “NASH” spider web, which illustrates steatohepatitis-like phenotype. This is a metaphor that genetic association can be better captured in a certain metabolic state, enabling efficient evaluation of genetic markers for common disorders like NASH. (Credit: Institute of Research, TMDU)

Researchers from Tokyo Medical and Dental University (TMDU) and Cincinnati Children’s Hospital Medical Center (CCHMC) find that a point mutation in the glucokinase regulatory protein gene protects against liver disease in nondiabetic patients but predisposes diabetic patients to nonalcoholic fatty liver disease. Context is known to influence many spheres. And now, researchers from Japan have found that a patients’ health context—that is, the other conditions a patient has—can determine whether a specific gene mutation is helpful or harmful. Researchers from Tokyo Medical and Dental University (TMDU) and Cincinnati Children’s Hospital Medical Center (CCHMC) have revealed that a genetic mutation with a controversial connection to liver disease confers different levels of risk depending on whether patients have diabetes.