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DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants

The association of preterm birth with obesity and metabolic syndrome later in life is well established. Although the biological mechanism for this association is poorly understood, epigenetic alterations of metabolic-related genes in early life may have important roles in metabolic dysfunction. Thus...

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Autores principales: Kwon, Eun Jin, Lee, Hye Ah, You, Young-Ah, Park, Hyesook, Cho, Su Jin, Ha, Eun Hee, Kim, Young Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008556/
https://www.ncbi.nlm.nih.gov/pubmed/27583872
http://dx.doi.org/10.1097/MD.0000000000004590
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author Kwon, Eun Jin
Lee, Hye Ah
You, Young-Ah
Park, Hyesook
Cho, Su Jin
Ha, Eun Hee
Kim, Young Ju
author_facet Kwon, Eun Jin
Lee, Hye Ah
You, Young-Ah
Park, Hyesook
Cho, Su Jin
Ha, Eun Hee
Kim, Young Ju
author_sort Kwon, Eun Jin
collection PubMed
description The association of preterm birth with obesity and metabolic syndrome later in life is well established. Although the biological mechanism for this association is poorly understood, epigenetic alterations of metabolic-related genes in early life may have important roles in metabolic dysfunction. Thus, we investigated the associations of DNA methylations of melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) with metabolic profiles in cord blood of term and preterm infants. We measured metabolic profiles in cord blood samples of 85 term and 85 preterm infants. DNA methylation and mRNA expression levels of MC4R and HNF4α in cord blood cells were quantified using pyrosequencing and real-time PCR. Triglyceride (TG) levels were grouped by percentile as low (<10th percentile), mid (11th–89th percentiles), and high (>90th percentile). A multiple linear regression model was used to assess the differential effects of DNA methylation on metabolic indices in cord blood between term and preterm infants. The beta-coefficients for associations between TG levels and methylation statuses of MC4R-CpG3 and HNF4α-CpG2 in the P1 promoter differed significantly between term and preterm infants (P = 0.04 and P = 0.003, respectively). DNA methylation statuses of MC4R-CpG3 and HNF4α–CpG2 in the P1 promoter were significantly lower in preterm infants in the high-TG group compared with those in the mid- and low-TG groups (P = 0.01). Notably, preterm infants in the high-TG group had higher TG levels in cord blood than term infants in the high-TG group (60.49 vs 54.57 mg/dL). In addition, MC4R and HNF4α expression levels were higher in preterm infants than in term infants (P < 0.05). Epigenetic alterations of the newly identified genes MC4R and HNF4α in early life might contribute to metabolic profile changes, especially increased TG levels, in the cord blood of preterm infants.
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spelling pubmed-50085562016-09-10 DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants Kwon, Eun Jin Lee, Hye Ah You, Young-Ah Park, Hyesook Cho, Su Jin Ha, Eun Hee Kim, Young Ju Medicine (Baltimore) 4400 The association of preterm birth with obesity and metabolic syndrome later in life is well established. Although the biological mechanism for this association is poorly understood, epigenetic alterations of metabolic-related genes in early life may have important roles in metabolic dysfunction. Thus, we investigated the associations of DNA methylations of melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) with metabolic profiles in cord blood of term and preterm infants. We measured metabolic profiles in cord blood samples of 85 term and 85 preterm infants. DNA methylation and mRNA expression levels of MC4R and HNF4α in cord blood cells were quantified using pyrosequencing and real-time PCR. Triglyceride (TG) levels were grouped by percentile as low (<10th percentile), mid (11th–89th percentiles), and high (>90th percentile). A multiple linear regression model was used to assess the differential effects of DNA methylation on metabolic indices in cord blood between term and preterm infants. The beta-coefficients for associations between TG levels and methylation statuses of MC4R-CpG3 and HNF4α-CpG2 in the P1 promoter differed significantly between term and preterm infants (P = 0.04 and P = 0.003, respectively). DNA methylation statuses of MC4R-CpG3 and HNF4α–CpG2 in the P1 promoter were significantly lower in preterm infants in the high-TG group compared with those in the mid- and low-TG groups (P = 0.01). Notably, preterm infants in the high-TG group had higher TG levels in cord blood than term infants in the high-TG group (60.49 vs 54.57 mg/dL). In addition, MC4R and HNF4α expression levels were higher in preterm infants than in term infants (P < 0.05). Epigenetic alterations of the newly identified genes MC4R and HNF4α in early life might contribute to metabolic profile changes, especially increased TG levels, in the cord blood of preterm infants. Wolters Kluwer Health 2016-09-02 /pmc/articles/PMC5008556/ /pubmed/27583872 http://dx.doi.org/10.1097/MD.0000000000004590 Text en Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved. http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-nc-sa/4.0
spellingShingle 4400
Kwon, Eun Jin
Lee, Hye Ah
You, Young-Ah
Park, Hyesook
Cho, Su Jin
Ha, Eun Hee
Kim, Young Ju
DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants
title DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants
title_full DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants
title_fullStr DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants
title_full_unstemmed DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants
title_short DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants
title_sort dna methylations of mc4r and hnf4α are associated with increased triglyceride levels in cord blood of preterm infants
topic 4400
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008556/
https://www.ncbi.nlm.nih.gov/pubmed/27583872
http://dx.doi.org/10.1097/MD.0000000000004590
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