AUTHOR=Kanoni Stavroula , Kumar Satish , Amerikanou Charalampia , Kurth Mary Jo , Stathopoulou Maria G. , Bourgeois Stephane , Masson Christine , Kannt Aimo , Cesarini Lucia , Kontoe Maria-Spyridoula , Milanović Maja , Roig Francisco J. , Beribaka Mirjana , Campolo Jonica , Jiménez-Hernández Nuria , Milošević Nataša , Llorens Carlos , Smyrnioudis Ilias , Francino M. Pilar , Milić Nataša , Kaliora Andriana C. , Trivella Maria Giovanna , Ruddock Mark W. , Medić-Stojanoska Milica , Gastaldelli Amalia , Lamont John , Deloukas Panos , Dedoussis George V. , Visvikis-Siest Sophie 

TITLE=Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.683028

DOI=10.3389/fimmu.2021.683028

ISSN=1664-3224

ABSTRACT=<p>Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m<sup>2</sup>) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI &gt; 35kg/m<sup>2</sup>) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (<italic>LSS)</italic> associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (<italic>MPC1)</italic> and the sphingolipid transporter-1 gene (<italic>SPNS1</italic>) associated with hemoglobin levels, the transforming growth factor‐beta‐induced gene (<italic>TGFBI</italic>) and the micro-RNA 129-1 (<italic>MIR129-1)</italic> associated with IL-6 and the granzyme B gene (<italic>GZMB</italic>) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, <uri xlink:href="http://www.clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.clinicaltrials.gov</uri>) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD.</p><sec><title>Clinical Trial Registration</title><p><uri xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</uri>, identifier NCT03135873.</p></sec>