Non-alcoholic fatty liver disease (NAFLD) is worldwide recognized as the most common cause of chronic liver disease. Current NAFLD clinical management relies on lifestyle change, nevertheless, the importance of the genetic make-up on liver damage and the possible interactions with diet are still poorly understood. The aim of the study was to evaluate the influence of the SH2B1 rs7359397 genetic variant on changes in body composition, metabolic status and liver health after 6-month energy-restricted treatment in overweight/obese subjects with NAFLD. In addition, gene-treatment interactions over the course of the intervention were examined.
The SH2B1 genetic variant was genotyped in 86 overweight/obese subjects with NAFLD from the FLiO study (Fatty Liver in Obesity study). Subjects were metabolically evaluated at baseline and at 6-months. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, a lipidomic test (OWL®-test) and specific blood liver biomarkers. Additionally, body composition, general biochemical markers and dietary intake were determined.
Both genotypes significantly improved their body composition, general metabolic status and liver health after following an energy-restricted strategy. Liver imaging techniques showed a greater decrease in liver fat content (− 44.3%, p < 0.001) and in serum ferritin levels (p < 0.001) in the carriers of the T allele after the intervention. Moreover, lipidomic analysis, revealed a higher improvement in liver status when comparing risk vs. no-risk genotype (p = 0.006 vs. p = 0.926, respectively). Gene-treatment interactions showed an increase in fiber intake and omega-3 fatty acid in risk genotype (p interaction = 0.056 and p interaction = 0.053, respectively), while a significant increase in MedDiet score was observed in both genotype groups (p = 0.020). Moreover, no-risk genotype presented a relevant decrease in hepatic iron as well as in MUFA intake (p = 0.047 and p = 0.034, respectively).
Subjects carrying the T allele of the rs7359397 polymorphism may benefit more in terms of hepatic health and liver status when prescribed an energy-restricted treatment, where a Mediterranean dietary pattern rich in fiber and other components such as omega-3 fatty acids might boost the benefits.
The Fatty Liver in Obesity was approved by the Research Ethics Committee of the University of Navarra and retrospectively registered (NCT03183193; www.clinicaltrials.gov); June 2017.
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American Association for the Study of Liver Diseases
American Heart Association
Atherogenic Index of Plasma
Body Mass Index
Dual-energy X-ray absorptiometry
European Association for the Study of the Liver
Food Frequency Questionnaire
Fatty Liver Index
Fatty liver in obesity
High density lipoprotein cholesterol
Homeostasis model assessment insulin resistance
Low-density lipoprotein cholesterol
- MedDiet Score:
Mediterranean Diet Score
Metabolic equivalent of the task
Magnetic resonance imaging
Monounsaturated fatty acid
Non-alcoholic fatty liver disease
- OWLiver® :
One Way Liver®
Polyunsaturated fatty acid
Saturated fatty acid
- SH2 :
- SH2B1 :
Src-homology-2 B adaptor protein 1
Single nucleotide polymorphism
- TyG index:
Triglycerides and Glucose Index
Visceral adipose tissue
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The authors are grateful to the volunteers of the study as well as Veronica Ciaurriz and to the nurses from the departments of Clinical Chemistry, Radiology, Internal Medicine and the Liver Unit of the Clinica Universidad de Navarra for their contribution to FLiO project. We also would like to thank Marta García Granero for statistical assistance. The pre-doctoral research grant to Nuria Pérez from the Centre for Nutrition Research of the University of Navarra is gratefully acknowledged. The tractor role from LABORATORIOS CINFA, S.A. and VISCOFAN S.A. for financial support of the Center for Nutrition Research as well as the support from the Government of Navarra are also appreciated. Finally, the authors wish to express their gratitude to the Government of Navarra, CIBERobn and Fundació La Marató de TV3 for the financial support.
This research was funded by the Health Department of the Government of Navarra (61/2015), CIBERobn (Physiopathology of Obesity and Nutrition) (CB12/03/3002) and Fundació La Marató de TV3 (201630.10).
Conflict of interest
The authors declare no conflict of interest concerning this research.
The present study was approved by the Research Ethics Committee of the University of Navarra on 24 April 2015 (ref. 54/2015) and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its latter amendments.
All participants gave written informed consent in a clinical interview for their participation in the study.
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Perez-Diaz-del-Campo, N., Marin-Alejandre, B.A., Cantero, I. et al. Differential response to a 6-month energy-restricted treatment depending on SH2B1 rs7359397 variant in NAFLD subjects: Fatty Liver in Obesity (FLiO) Study. Eur J Nutr (2021). https://doi.org/10.1007/s00394-020-02476-x
- Gene-treatment interaction
- Energy-restricted diet