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.

Nuria Perez-Diaz-Del-Campo,J Ignacio Monreal,J Alfredo Martinez,Mariana Elorz,Itziar Abete,José Ignacio Herrero,Bertha Araceli Marin-Alejandre,Fermín I Milagro,Josep A Tur,Alberto Benito-Boillos,Jose I Riezu-Boj,M Angeles Zulet

doi:10.3390/diagnostics11061083

Abstract

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. The pathogenesis of NAFLD is complex; available data reveal 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-month weight loss nutritional treatment. 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. A pre-designed panel of 95 genetic variants related to obesity and weight loss was applied and analyzed. 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. Overall, 23 SNPs were independently associated with the change in 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 in 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). 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.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in high-income countries, affecting more than 25% of the population [1]
The intervention had a duration of 24 months and the participants were randomly assigned to the American Heart Association (AHA) or the Fatty Liver in Obesity (FLiO) group [34]
Analyzing variables associated with liver injury, statistical differences were observed in the fatty liver index (76.0 vs. 89.6)

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in high-income countries, affecting more than 25% of the population [1]. The NAFLD etiology is multifactorial and yet incompletely understood, but appears as determined by the combination of environmental factors, such as excessive adiposity or the presence of type 2 diabetes (T2D) as well as the accumulation of intrahepatic lipids, alterations of energy metabolism, insulin resistance and inflammatory processes, where the genetic make-up may emerge [1,4]. Other factors such as obesity and a sedentary lifestyle, together with metabolic syndrome features and ethnicity, influence the risk of NAFLD [5]. The decision about when to perform this screening remains controversial [2], being necessary the search for less invasive methods for screening patients suspected of this disease [6,7,8,9]

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