Abstract
BackgroundA single nucleotide polymorphism (SNP), the rs738409, in the patatin like phospholipase 3 gene (PNPLA3) has been recently associated with increased hepatic steatosis and ALT levels in adults and children. Given the potential role of PNPLA3 in fatty liver development, we aimed to explore whether the influence of PNPLA3 genotype on hepatic fat in obese youth might be modulated by dietary factors such as essential omega polyunsaturated fatty acids (PUFA) intake.Materials and MethodsWe studied 127 children and adolescents (56 boys, 71 girls; 58 Caucasians; 30 African Americans and 39 Hispanics; mean age 14.7±3.3; mean BMI 30.7±7.2). The dietary composition was assessed by the Nutrition Data System for Research (NDS-R version 2011). The patients underwent a MRI study to assess the liver fat content (HFF%), ALT measurement and the genotyping of the rs738409 SNP by automatic sequencing.ResultsAs previously observed, HFF% and ALT levels varied according to the genotype in each ethnicity. ALT levels and HFF% were significantly influenced by the interaction between genotype and omega-6/omega-3 PUFA ratio (n-6/n-3), p = 0.003 and p = 0.002, respectively. HFF% and ALT levels were, in fact, related to the n-6/n-3 consumption only in subjects homozygote for the G allele of the rs738409 (r2 = 0.45, p = 0.001 and r2 = 0.40, p = 0.006, respectively).ConclusionsThese findings suggest that the association of a high dietary n-6/n-3 PUFA with fatty liver and liver damage in obese youths may be driven by a predisposing genotype.
Highlights
Non alcoholic fatty liver disease (NAFLD) is emerging as one of the most common complications of childhood obesity
ALT levels and HFF% were significantly influenced by the interaction between genotype and omega-6/omega-3 polyunsaturated fatty acids (PUFA) ratio (n-6/n-3), p = 0.003 and p = 0.002, respectively
These findings suggest that the association of a high dietary n-6/n-3 PUFA with fatty liver and liver damage in obese youths may be driven by a predisposing genotype
Summary
Non alcoholic fatty liver disease (NAFLD) is emerging as one of the most common complications of childhood obesity It is associated with and predicts the metabolic syndrome, independent of overall obesity [1]. A non-synonymous SNP (rs738409), characterized by a C to G substitution encoding an isoleucine to methionine substitution at the amino acid position 148 in the patatin like phospholipase 3 gene (PNPLA3), was found to be associated with hepatic steatosis in a multiethnic cohort of adults [2] as well as in children [3,4]. It has been shown that this variant interacts with environmental stressors, such as obesity [5,6] and alcohol consumption [7], that induce fatty liver These stressors seem to uncover the association between the rs738409 minor allele (G) and hepatic injury in populations in whom it is otherwise covert [8]. Given the potential role of PNPLA3 in fatty liver development, we aimed to explore whether the influence of PNPLA3 genotype on hepatic fat in obese youth might be modulated by dietary factors such as essential omega polyunsaturated fatty acids (PUFA) intake
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