CHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity

CHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity

Adela Chirita-Emandi,1,2,* Costela Lacrimioara Serban,2,3,* Corina Paul,4,5,* Nicoleta Andreescu,1,2 Iulian Velea,4,5 Alexandra Mihailescu,1 Vlad Serafim,1,6 Diana-Andreea Tiugan,1 Paul Tutac,1 Cristian Zimbru,1,7 Maria Puiu,1,2 Mihai Dinu Niculescu1,8 1Department of Microscopic Morphology - Genetic...

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Autores principales: Chirita-Emandi A, Serban CL, Paul C, Andreescu N, Velea I, Mihailescu A, Serafim V, Tiugan DA, Tutac P, Zimbru C, Puiu M, Niculescu MD
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2020
Materias:
insulin-resistance
obesity
gene-gene interaction
chdh-pnpla3
choline
children.
Specialties of internal medicine
RC581-951
Acceso en línea:https://doaj.org/article/04881700b87948d8983adfb4f9cd7f36
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id oai:doaj.org-article:04881700b87948d8983adfb4f9cd7f36
record_format dspace
institution DOAJ
collection DOAJ
language EN
topic insulin-resistance
obesity
gene-gene interaction
chdh-pnpla3
choline
children.
Specialties of internal medicine
RC581-951
spellingShingle insulin-resistance
obesity
gene-gene interaction
chdh-pnpla3
choline
children.
Specialties of internal medicine
RC581-951
Chirita-Emandi A
Serban CL
Paul C
Andreescu N
Velea I
Mihailescu A
Serafim V
Tiugan DA
Tutac P
Zimbru C
Puiu M
Niculescu MD
CHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity
description Adela Chirita-Emandi,1,2,* Costela Lacrimioara Serban,2,3,* Corina Paul,4,5,* Nicoleta Andreescu,1,2 Iulian Velea,4,5 Alexandra Mihailescu,1 Vlad Serafim,1,6 Diana-Andreea Tiugan,1 Paul Tutac,1 Cristian Zimbru,1,7 Maria Puiu,1,2 Mihai Dinu Niculescu1,8 1Department of Microscopic Morphology - Genetics, Center of Genomic Medicine, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 2Regional Center of Medical Genetics Timis, Clinical Emergency Hospital for Children “Louis Turcanu”, Timisoara, Romania; 3Department of Functional Sciences, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 4Pediatrics Department – Pediatrics Discipline II, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 5Pediatrics, Endocrinology and Diabetes Department, Clinic II Pediatrics, “Pius Branzeu” Clinical Emergency County Hospital, Timisoara, Romania; 6The National Institute of Research and Development for Biological Sciences, Bucharest, Romania; 7Department of Automation and Applied Informatics, Politehnica University of Timisoara, Timisoara, Romania; 8Advanced Nutrigenomics, Cary, NC 27511, USA*These authors contributed equally to this workCorrespondence: Nicoleta AndreescuDepartment of Microscopic Morphology - Genetics, Center of Genomic Medicine, University of Medicine and Pharmacy “Victor Babes”, Timisoara, RomaniaEmail andreescu.nicoleta@umft.roIntroduction: Insulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention.Purpose: To evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity.Methods: One hundred fifty-three children with obesity (73 girls), aged 7– 18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene–gene interaction effects were assessed using Multiple Data Reduction Software.Results: Sixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes CHDH(rs12676) and PNPLA3(rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model.Conclusion: The interaction between genotypes in CHDH and PNPLA3 genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.Keywords: insulin-resistance, obesity, gene–gene interaction, CHDH-PNPLA3, choline, children
format article
author Chirita-Emandi A
Serban CL
Paul C
Andreescu N
Velea I
Mihailescu A
Serafim V
Tiugan DA
Tutac P
Zimbru C
Puiu M
Niculescu MD
author_facet Chirita-Emandi A
Serban CL
Paul C
Andreescu N
Velea I
Mihailescu A
Serafim V
Tiugan DA
Tutac P
Zimbru C
Puiu M
Niculescu MD
author_sort Chirita-Emandi A
title CHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity
title_short CHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity
title_full CHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity
title_fullStr CHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity
title_full_unstemmed CHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity
title_sort chdh-pnpla3 gene–gene interactions predict insulin resistance in children with obesity
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/04881700b87948d8983adfb4f9cd7f36
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spelling oai:doaj.org-article:04881700b87948d8983adfb4f9cd7f362021-12-02T12:57:04ZCHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity1178-7007https://doaj.org/article/04881700b87948d8983adfb4f9cd7f362020-11-01T00:00:00Zhttps://www.dovepress.com/chdh-pnpla3-genendashgene-interactions-predict-insulin-resistance-in-c-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Adela Chirita-Emandi,1,2,* Costela Lacrimioara Serban,2,3,* Corina Paul,4,5,* Nicoleta Andreescu,1,2 Iulian Velea,4,5 Alexandra Mihailescu,1 Vlad Serafim,1,6 Diana-Andreea Tiugan,1 Paul Tutac,1 Cristian Zimbru,1,7 Maria Puiu,1,2 Mihai Dinu Niculescu1,8 1Department of Microscopic Morphology - Genetics, Center of Genomic Medicine, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 2Regional Center of Medical Genetics Timis, Clinical Emergency Hospital for Children “Louis Turcanu”, Timisoara, Romania; 3Department of Functional Sciences, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 4Pediatrics Department – Pediatrics Discipline II, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 5Pediatrics, Endocrinology and Diabetes Department, Clinic II Pediatrics, “Pius Branzeu” Clinical Emergency County Hospital, Timisoara, Romania; 6The National Institute of Research and Development for Biological Sciences, Bucharest, Romania; 7Department of Automation and Applied Informatics, Politehnica University of Timisoara, Timisoara, Romania; 8Advanced Nutrigenomics, Cary, NC 27511, USA*These authors contributed equally to this workCorrespondence: Nicoleta AndreescuDepartment of Microscopic Morphology - Genetics, Center of Genomic Medicine, University of Medicine and Pharmacy “Victor Babes”, Timisoara, RomaniaEmail andreescu.nicoleta@umft.roIntroduction: Insulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention.Purpose: To evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity.Methods: One hundred fifty-three children with obesity (73 girls), aged 7– 18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene–gene interaction effects were assessed using Multiple Data Reduction Software.Results: Sixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes CHDH(rs12676) and PNPLA3(rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model.Conclusion: The interaction between genotypes in CHDH and PNPLA3 genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.Keywords: insulin-resistance, obesity, gene–gene interaction, CHDH-PNPLA3, choline, childrenChirita-Emandi ASerban CLPaul CAndreescu NVelea IMihailescu ASerafim VTiugan DATutac PZimbru CPuiu MNiculescu MDDove Medical Pressarticleinsulin-resistanceobesitygene-gene interactionchdh-pnpla3cholinechildren.Specialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 4483-4494 (2020)

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