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

Chiara Zusi, Alessandro Mantovani, Francesca Olivieri, Anita Morandi, Massimiliano Corradi, Emanuele Miraglia Del Giudice, Marco Dauriz, Luca Valenti, Christopher D. Byrne, Giovanni Targher, Claudio Maffeis

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)1586-1592
JournalDigestive and Liver Disease
Volume51
Issue number11
DOIs
Publication statusPublished - Jan 1 2019

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Liver
Single Nucleotide Polymorphism
Non-alcoholic Fatty Liver Disease
Genetic Loci
Lipid Metabolism
Liver Diseases
Ultrasonography
Oxidative Stress
Pediatrics
Polymerase Chain Reaction
Population

Keywords

  • Genetics
  • NAFLD
  • Nonalcoholic fatty liver disease
  • Obesity
  • Pediatrics

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Zusi, C., Mantovani, A., Olivieri, F., Morandi, A., Corradi, M., Miraglia Del Giudice, E., ... Maffeis, C. (2019). Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents. Digestive and Liver Disease, 51(11), 1586-1592. https://doi.org/10.1016/j.dld.2019.05.029

Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents. / Zusi, Chiara; Mantovani, Alessandro; Olivieri, Francesca; Morandi, Anita; Corradi, Massimiliano; Miraglia Del Giudice, Emanuele; Dauriz, Marco; Valenti, Luca; Byrne, Christopher D.; Targher, Giovanni; Maffeis, Claudio.

In: Digestive and Liver Disease, Vol. 51, No. 11, 01.01.2019, p. 1586-1592.

Research output: Contribution to journalArticle

Zusi, C, Mantovani, A, Olivieri, F, Morandi, A, Corradi, M, Miraglia Del Giudice, E, Dauriz, M, Valenti, L, Byrne, CD, Targher, G & Maffeis, C 2019, 'Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents', Digestive and Liver Disease, vol. 51, no. 11, pp. 1586-1592. https://doi.org/10.1016/j.dld.2019.05.029
Zusi, Chiara ; Mantovani, Alessandro ; Olivieri, Francesca ; Morandi, Anita ; Corradi, Massimiliano ; Miraglia Del Giudice, Emanuele ; Dauriz, Marco ; Valenti, Luca ; Byrne, Christopher D. ; Targher, Giovanni ; Maffeis, Claudio. / Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents. In: Digestive and Liver Disease. 2019 ; Vol. 51, No. 11. pp. 1586-1592.
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T1 - Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents

AU - Zusi, Chiara

AU - Mantovani, Alessandro

AU - Olivieri, Francesca

AU - Morandi, Anita

AU - Corradi, Massimiliano

AU - Miraglia Del Giudice, Emanuele

AU - Dauriz, Marco

AU - Valenti, Luca

AU - Byrne, Christopher D.

AU - Targher, Giovanni

AU - Maffeis, Claudio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Genetics

KW - NAFLD

KW - Nonalcoholic fatty liver disease

KW - Obesity

KW - Pediatrics

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