Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.

There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later developm...

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Autores principales:	Marina Rangel, Jéssica Cassilla dos Santos, Paula Helena Lima Ortiz, Mario Hirata, Miriam Galvonas Jasiulionis, Ronaldo C Araujo, Daniela Filippini Ierardi, Maria do Carmo Franco
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/99e4b846d67046c0b74c67210cfa476a
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spelling	oai:doaj.org-article:99e4b846d67046c0b74c67210cfa476a2021-11-25T06:02:31ZModification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.1932-620310.1371/journal.pone.0106138https://doaj.org/article/99e4b846d67046c0b74c67210cfa476a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25170764/?tool=EBIhttps://doaj.org/toc/1932-6203There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P<0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (P<0.001) and systolic blood pressure levels (P<0.001). We also observed that the methylation level was significantly lower in LBW children who are carriers of the DD genotype compared to NBW children with DD genotype (P<0.024). In conclusion, we are able to demonstrate that the hypomethylation in the 3 CpG sites of ACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels.Marina RangelJéssica Cassilla dos SantosPaula Helena Lima OrtizMario HirataMiriam Galvonas JasiulionisRonaldo C AraujoDaniela Filippini IerardiMaria do Carmo FrancoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e106138 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marina Rangel Jéssica Cassilla dos Santos Paula Helena Lima Ortiz Mario Hirata Miriam Galvonas Jasiulionis Ronaldo C Araujo Daniela Filippini Ierardi Maria do Carmo Franco Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.
description	There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P<0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (P<0.001) and systolic blood pressure levels (P<0.001). We also observed that the methylation level was significantly lower in LBW children who are carriers of the DD genotype compared to NBW children with DD genotype (P<0.024). In conclusion, we are able to demonstrate that the hypomethylation in the 3 CpG sites of ACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels.
format	article
author	Marina Rangel Jéssica Cassilla dos Santos Paula Helena Lima Ortiz Mario Hirata Miriam Galvonas Jasiulionis Ronaldo C Araujo Daniela Filippini Ierardi Maria do Carmo Franco
author_facet	Marina Rangel Jéssica Cassilla dos Santos Paula Helena Lima Ortiz Mario Hirata Miriam Galvonas Jasiulionis Ronaldo C Araujo Daniela Filippini Ierardi Maria do Carmo Franco
author_sort	Marina Rangel
title	Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.
title_short	Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.
title_full	Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.
title_fullStr	Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.
title_full_unstemmed	Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.
title_sort	modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ace gene promoter.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/99e4b846d67046c0b74c67210cfa476a
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Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.

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