The Protective Effect of FOXO3 rs2802292 G-Allele on Food Intake in a Southern Italian Cohort Affected by MASLD

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a cluster of conditions characterized by accumulations of fat, metabolic factors such as obesity, diabetes and high cholesterol. MASLD is now the leading cause of chronic liver disease worldwide, with a rapidly increasing trend. We aimed to demonstrate that genetic variants of rs2802292 SNP can influence the development of MASLD even after many years. Methods: We studied 650 participants from the NUTRIHEP cohort, both at baseline (2005-2006) and at first recall (2014-2018), and genotyped rs2802292. The validated European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire was administered during the visit, and each single food was assigned to one of 33 groups. Results: Associations of food intake at baseline with MASLD were found in the first recall, for each genotype, GG, GT, and TT, and several covariates were used to adjust models. Dressing fats other than olive oil resulted protection against MASLD in GG subjects, whereas seed oil, juices, and spirits resulted in protection against MASLD for GT subjects. An increased risk of MASLD was found for subjects with the TT genotype for white meat intake (OR = 1.018, p = 0.031, 1.002 to 1.035 95% C.I.), ready-to-eat dishes (OR = 1.015, p = 0.033, 1.001 to 1.029 95% C.I.), processed meat (OR = 1.093, p = 0.003, 1.031 to 1.158 95% C.I.), and processed fish (OR = 1.085, p = 0.037, 1.005 to 1.172 95% C.I.). Conclusions: Subjects with the TT genotype had a higher risk of developing MASLD than subjects with other genotypes. A healthier lifestyle is important to counteract liver disease.