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Pediatric Non-Alcoholic Fatty Liver Disease Is Affected by Genetic Variants Involved in Lifespan/Healthspan

Crudele, A, Dato, S, Re, OL, Maugeri, A, Sanna, P, Giallongo, S, Oben, J, Panera, N, De Rango, F, Mosca, A, Rose, G, Passarino, G, Alisi, A and Vinciguerra, M (2021) Pediatric Non-Alcoholic Fatty Liver Disease Is Affected by Genetic Variants Involved in Lifespan/Healthspan. Journal of Pediatric Gastroenterology and Nutrition, 73 (2). pp. 161-168. ISSN 0277-2116

Pediatric Non-Alcoholic Fatty Liver Disease Is Affected by Genetic Variants Involved in Lifespan Healthspan.pdf - Published Version
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Open Access URL: https://doi.org/10.1097/MPG.0000000000003123 (Published version)


OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in both adults and children. Along with obesity and metabolic syndrome, genetic predisposition influences the progression of NAFLD. Here, we investigated the effect of lifespan/healthspan-related single nucleotide polymorphisms (SNPs) on metabolically associated fatty liver disease in children.
METHODS: We evaluated the impact of 10 SNPs involved in both human liver/metabolic diseases and healthspan (interleukin-6 [IL-6] rs1800795, antisense non coding RNA in the INK4 locus (ANRIL) rs1556516, SH2B3/ATXN2 rs7137828, FURIN rs17514846, TP53 rs1042522, APOC3 rs2542052, KL rs9536314, KL rs9527025, SIRT6 rs107251, FOXO3 rs2802292) on NAFLD-related metabolic and liver features in 177 pediatric patients with biopsy-proven NAFLD, by comparing them to 146 healthy controls. We then applied a multidimensional reduction (MDR) case-control analysis of SNP-SNP interactions, to identify the joint effect of analyzed SNPs in predicting NAFLD and associated features.
RESULTS: Discrete SNPs were significantly associated with individual metabolic NAFLD features, but none of them significantly associated with NAFLD diagnosis. By testing potential synergies using the MDR approach, the best combination to diagnose NAFLD (P = 0.0011) resulted in the one encompassing IL-6 rs1800795 and ANRIL rs1556516. Consistently, the risk combinations suggested by SNP-SNP analysis strongly associated with a higher level of fasting plasma blood glucose level (P = 0.024).
CONCLUSION: In conclusion, here we demonstrated a synergic interaction between IL-6 rs1800795 and ANRIL rs1556516 in the diagnosis of NAFLD, and NAFLD-associated hyperglycemia in children. Larger studies are required to confirm our findings and to elucidate mechanisms by which the genetic interaction between these two genes influences healthspan in pediatric NAFLD.

Item Type: Article
Uncontrolled Keywords: Liver; Humans; Genetic Predisposition to Disease; Sirtuins; Longevity; Polymorphism, Single Nucleotide; Adult; Child; Non-alcoholic Fatty Liver Disease; Adult; Child; Genetic Predisposition to Disease; Humans; Liver; Longevity; Non-alcoholic Fatty Liver Disease; Polymorphism, Single Nucleotide; Sirtuins; 11 Medical and Health Sciences; Gastroenterology & Hepatology
Subjects: R Medicine > R Medicine (General)
R Medicine > RJ Pediatrics
Divisions: Nursing & Allied Health
Publisher: Lippincott, Williams & Wilkins
SWORD Depositor: A Symplectic
Date Deposited: 24 Jan 2023 12:32
Last Modified: 24 Jan 2023 12:45
DOI or ID number: 10.1097/MPG.0000000000003123
URI: https://researchonline.ljmu.ac.uk/id/eprint/18723
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