Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents
Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents
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.
1586-1592
Zusi, Chiara
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Mantovani, Alessandro
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Olivieri, Francesca
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Morandi, Anita
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Corradi, Massimiliano
ebc82bef-e194-47ab-a722-a96401863870
Miraglia Del Giudice, Emanuele
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Dauriz, Marco
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Valenti, Luca
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Byrne, Christopher
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Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Maffeis, Claudio
52914599-a576-4582-a1df-d9893e0713f5
1 November 2019
Zusi, Chiara
7669c189-4134-4fd9-a9fc-ef4c6e3a2734
Mantovani, Alessandro
19fc8a1f-60fe-403a-b70e-6b6884929e03
Olivieri, Francesca
4dcba65a-d491-4362-a496-33df1dec42de
Morandi, Anita
f2d77c88-e978-4992-9af0-6c572ab9ed55
Corradi, Massimiliano
ebc82bef-e194-47ab-a722-a96401863870
Miraglia Del Giudice, Emanuele
1fa637d9-e1d0-430e-bbe4-ce44fc209425
Dauriz, Marco
00f1b574-5b90-4ecd-b2fc-90d489122a20
Valenti, Luca
da6d620f-9e53-404e-bc22-719ce58a743b
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Maffeis, Claudio
52914599-a576-4582-a1df-d9893e0713f5
Zusi, Chiara, Mantovani, Alessandro, Olivieri, Francesca, Morandi, Anita, Corradi, Massimiliano, Miraglia Del Giudice, Emanuele, Dauriz, Marco, Valenti, Luca, Byrne, Christopher, Targher, Giovanni and Maffeis, Claudio
(2019)
Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents.
Digestive and Liver Disease, 51 (11), .
(doi:10.1016/j.dld.2019.05.029).
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.
Text
Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents
- Accepted Manuscript
More information
Accepted/In Press date: 28 May 2019
e-pub ahead of print date: 27 June 2019
Published date: 1 November 2019
Identifiers
Local EPrints ID: 431389
URI: http://eprints.soton.ac.uk/id/eprint/431389
ISSN: 1590-8658
PURE UUID: 351a63e3-6d53-4a8f-8f2f-8f7044357ad0
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Date deposited: 31 May 2019 16:30
Last modified: 16 Mar 2024 07:53
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Contributors
Author:
Chiara Zusi
Author:
Alessandro Mantovani
Author:
Francesca Olivieri
Author:
Anita Morandi
Author:
Massimiliano Corradi
Author:
Emanuele Miraglia Del Giudice
Author:
Marco Dauriz
Author:
Luca Valenti
Author:
Giovanni Targher
Author:
Claudio Maffeis
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