Potential contribution of GST-T1 and GST-M1 polymorphisms in the onset of hepatic steatosis: from radiological to molecular and medico-legal analyses

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease the world, and it is characterized by an excessive hepatic fat accumulation in more than the 5% of hepatocytes documented by histology in absence of alcohol consumption. It is a multifactorial pathology, where genetic component plays a fundamental role: the loss-of-function polymorphisms of genes coding for Glutathione S-transferases would predispose to the pathology onset, also in absence of other risk factors. The aim of the study is to evaluate the relation between the “NULL” GST-T1 and GST-M1 polymorphisms and the onset of NAFLD. Methods: A group of 117 "apparently healthy" caucasian volunteers, selected from a larger population through the analysis of previously administered short questionnaires, underwent both MRI-PDFF (Magnetic Resonance Imaging - Proton Density Fat Fraction) and buccal swabs: the aim was to identify the possible presence of hepatic steatosis and the possible presence of the aforementioned "NULL" polymorphisms of interest. Results: a statistically significant association between GST-T1 and GST-M1 “NULL” genotype and the probability of developing NAFLD has been identified. In particular, GST-T1 “NULL” genotype has been associated with a greater probability of developing steatosis in early age, while the GST-M1 “NULL” genotype seems to increase the risk of developing a higher grade of steatosis. No statistically significant correlations between “NULL” genotype and sex have been detected. Discussion: Among the numerous risk factors capable of predisposing to the NAFLD onset and progression, the genetic ones seem to play an important role. In particular, GST-T1 and GST-M1 "NULL" polymorphisms would appear to acquire ever greater importance, as their loss of function results in an increase of oxidative stress. At high concentrations, ROS can determine oxidative modifications of cellular macromolecules, such as lipids, determining their accumulation into hepatocytes. The study also highlighted the importance of MRI-PDFF for the hepatic steatosis diagnosis: this method let the acquisition of data comparable to those of conventional biopsy, but, unlike this, it permits the entire liver parenchyma to be visualized. Conclusion: A statistically significant correlation between the presence of the GST-T1 and GST-M1 “NULL” genotypes and the presence of hepatic steatosis has been found.