Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents

Autor: Massimiliano Corradi, Francesca Olivieri, Claudio Maffeis, Giovanni Targher, Marco Dauriz, Christopher D. Byrne, Chiara Zusi, Alessandro Mantovani, Anita Morandi, Luca Valenti, Emanuele Miraglia del Giudice
Přispěvatelé: Zusi, C., Mantovani, A., Olivieri, F., Morandi, A., Corradi, M., Miraglia Del Giudice, E., Dauriz, M., Valenti, L., Byrne, C. D., Targher, G., Maffeis, C.
Rok vydání: 2019
Předmět:
Male
Pediatric Obesity
Severity of Illness Index
Pediatrics
Gastroenterology
Liver disease
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Risk Factors
Nonalcoholic fatty liver disease
Medicine
Child
Membrane Protein
Multivariate Analysi
Pediatric
Genetics
NAFLD
Obesity
Italy
Liver
030220 oncology & carcinogenesis
Cohort
Regression Analysis
Female
030211 gastroenterology & hepatology
Human
medicine.medical_specialty
Adolescent
Single-nucleotide polymorphism
Polymorphism
Single Nucleotide
Regression Analysi
03 medical and health sciences
Genetic
Internal medicine
Humans
Genetic Predisposition to Disease
Genotyping
Adaptor Proteins
Signal Transducing
Hepatology
business.industry
Risk Factor
Membrane Proteins
Lipase
medicine.disease
Genetic Loci
Multivariate Analysis
Steatosis
business
TM6SF2
Zdroj: Digestive and Liver Disease. 51:1586-1592
ISSN: 1590-8658
DOI: 10.1016/j.dld.2019.05.029
Popis: BackgroundNonalcoholic 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.AimsWe 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.MethodsWe 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.ResultsThe 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).ConclusionsNAFLD 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.
Databáze: OpenAIRE
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