Three different genetic risk scores based on Fatty Liver Index, Magnetic Resonance Imaging and lipidomic for a nutrigenetic personalized management of NAFLD: the Fatty Liver in Obesity study

Abstract

Background Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. The pathogenesis of NAFLD is complex where available data unveils that genetics and ascribed interactions with environmental factors may play an important role in the development of this morbid condition. The purpose of this investigation was to assess genetic and non-genetic determinants putatively involved in the onset and progression of NAFLD after a 6-months weight-loss nutritional treatment. Methods A group of 86 overweight/obese subjects with NAFLD from the Fatty Liver in Obesity (FLiO) study were enrolled and metabolically evaluated at baseline and after 6-months. Also, a total of 95 single nucleotide polymorphisms (SNPs) related to obesity and weight loss were analyzed by a targeted next-generation sequencing system. Three genetic risk scores (GRS) concerning the improvement on hepatic health evaluated by minimally invasive methods such as the Fatty Liver Index (FLI) (GRSFLI), lipidomic-OWLiver®-test (GRSOWL) and Magnetic Resonance Imaging (MRI) (GRSMRI), were derived by adding the risk alleles genotypes. Body composition, liver injury-related markers and dietary intake were also monitored. Results Overall, 26 SNPs were independently associated with the change on FLI, 16 SNPs with OWLiver®-test and 8 SNPs with MRI, which were specific for every diagnosis tool. After adjusting for gender, age and other related predictors (insulin resistance, inflammatory biomarkers and dietary intake at baseline) the calculated GRSFLI, GRSOWL and GRSMRI were major contributors of the improvement on hepatic status. Thus, fitted linear regression models showed a variance of 53% (adj. R2 = 0.53) in hepatic functionality (FLI), 16% (adj. R2 = 0.16) in lipidomic metabolism (OWLiver®-test) and 34% (adj. R2 = 0.34) in liver fat content (MRI). Conclusion These results demonstrate that three different genetic scores can be useful for the personalized management of NAFLD, whose treatment must rely on specific dietary recommendations guided by the measurement of specific genetic biomarkers. Trial registration: The FLiO study: Fatty Liver in Obesity study, NCT03183193. Registered 12 June 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03183193