Chiara Zusi1, Alessandro Mantovani2, Francesca Olivieri3, Anita Morandi3, Massimiliano Corradi3, Emanuele Miraglia Del Giudice4, Marco Dauriz2, Luca Valenti5, Christopher D Byrne6, Giovanni Targher2, Claudio Maffeis7. 1. Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgery, Dentistry, Pediatrics and Gynaecology, University Hospital of Verona, Verona, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University Hospital of Verona, Verona, Italy. 2. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University Hospital of Verona, Verona, Italy. 3. Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgery, Dentistry, Pediatrics and Gynaecology, University Hospital of Verona, Verona, Italy. 4. Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy. 5. Department of Pathophysiology and Transplantation, University of Milan and Translational Medicine and Hepatology - Transfusional Center, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico Milano, Milan, Italy. 6. Nutrition and Metabolism, Faculty of Medicine, University of Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK. 7. Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgery, Dentistry, Pediatrics and Gynaecology, University Hospital of Verona, Verona, Italy. Electronic address: claudio.maffeis@univr.it.
Abstract
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in children and adolescents in Western countries. Complex traits arise from the interplay between environmental and genetic factors in the pathogenesis of NAFLD. AIMS: We examined the association between NAFLD and eleven single nucleotide polymorphisms (SNPs) at genetic loci potentially associated with liver damage (GCKR, MBOAT7, GPR120), oxidative stress (SOD2), lipid metabolism (PNPLA3, TM6SF2, LPIN1, ELOVL2, FADS2, MTTP) and fibrogenesis (KLF6) in a paediatric population. A genetic risk score (GRS) was performed taking into account both these SNPs and clinical risk factors. METHODS: We recruited a cohort of 514 obese children and adolescents (mean age [±SD]: 11.2 ± 2.8 years, z-BMI 3.3 ± 0.8). NAFLD was identified by ultrasonography. Genotyping was performed by TaqMan-based RT-PCR system. RESULTS: The overall prevalence of NAFLD was 67.5% (347 patients). Among the eleven genotyped SNPs, the genetic variants in TM6SF2 rs58542926 (OR = 4.13, p = 0.002), GCKR rs1260326 (OR = 1.53, p = 0.003), PNPLA3 rs738409 (OR = 1.58, p = 0.004) and ELOVL2 rs2236212 (OR = 1.34, p = 0.047) were significantly associated with a higher risk of NAFLD. Addition of a 11-polymorphism GRS to established clinical risk factors significantly (albeit modestly) improved the discriminatory capability of the regression model for predicting the risk of NAFLD (with SNPs C-statistic 0.81 [95%CI 0.75-0.88] vs. 0.77 [0.70-0.84] without SNPs; p = 0.047). CONCLUSIONS: NAFLD was strongly associated with three genetic variants, TM6SF2 rs58542926, PNPLA3 rs738409 and GCKR rs1260326, and more slightly with ELOVL2 rs2236212, in obese children and adolescents. Addition of a 11-polymorphism GRS to clinical risk factors improved the predictability of NAFLD.
BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in children and adolescents in Western countries. Complex traits arise from the interplay between environmental and genetic factors in the pathogenesis of NAFLD. AIMS: We examined the association between NAFLD and eleven single nucleotide polymorphisms (SNPs) at genetic loci potentially associated with liver damage (GCKR, MBOAT7, GPR120), oxidative stress (SOD2), lipid metabolism (PNPLA3, TM6SF2, LPIN1, ELOVL2, FADS2, MTTP) and fibrogenesis (KLF6) in a paediatric population. A genetic risk score (GRS) was performed taking into account both these SNPs and clinical risk factors. METHODS: We recruited a cohort of 514 obesechildren and adolescents (mean age [±SD]: 11.2 ± 2.8 years, z-BMI 3.3 ± 0.8). NAFLD was identified by ultrasonography. Genotyping was performed by TaqMan-based RT-PCR system. RESULTS: The overall prevalence of NAFLD was 67.5% (347 patients). Among the eleven genotyped SNPs, the genetic variants in TM6SF2rs58542926 (OR = 4.13, p = 0.002), GCKRrs1260326 (OR = 1.53, p = 0.003), PNPLA3rs738409 (OR = 1.58, p = 0.004) and ELOVL2rs2236212 (OR = 1.34, p = 0.047) were significantly associated with a higher risk of NAFLD. Addition of a 11-polymorphism GRS to established clinical risk factors significantly (albeit modestly) improved the discriminatory capability of the regression model for predicting the risk of NAFLD (with SNPs C-statistic 0.81 [95%CI 0.75-0.88] vs. 0.77 [0.70-0.84] without SNPs; p = 0.047). CONCLUSIONS: NAFLD was strongly associated with three genetic variants, TM6SF2rs58542926, PNPLA3rs738409 and GCKRrs1260326, and more slightly with ELOVL2rs2236212, in obesechildren and adolescents. Addition of a 11-polymorphism GRS to clinical risk factors improved the predictability of NAFLD.
Authors: Sabrina Xin Zi Quek; Eunice Xiang-Xuan Tan; Yi Ping Ren; Mark Muthiah; Evelyn Xiu Ling Loo; Elizabeth Huiwen Tham; Kewin Tien Ho Siah Journal: World J Hepatol Date: 2022-06-27
Authors: Simona Riccio; Rosa Melone; Caterina Vitulano; Pierfrancesco Guida; Ivan Maddaluno; Stefano Guarino; Pierluigi Marzuillo; Emanuele Miraglia Del Giudice; Anna Di Sessa Journal: World J Clin Pediatr Date: 2022-03-23