Cargando…

LINE-1 methylation status and its association with tetralogy of fallot in infants

BACKGROUND: Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and play an important role in maintaining genomic stability and gene expression. To derive insight into the association between genome-wide methylation status and tet...

Descripción completa

Detalles Bibliográficos
Autores principales: Sheng, Wei, Wang, Huijun, Ma, Xiaojing, Qian, Yanyan, Zhang, Ping, Wu, Yao, Zheng, Fengyun, Chen, Long, Huang, Guoying, Ma, Duan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408368/
https://www.ncbi.nlm.nih.gov/pubmed/22672592
http://dx.doi.org/10.1186/1755-8794-5-20
_version_ 1782239446219882496
author Sheng, Wei
Wang, Huijun
Ma, Xiaojing
Qian, Yanyan
Zhang, Ping
Wu, Yao
Zheng, Fengyun
Chen, Long
Huang, Guoying
Ma, Duan
author_facet Sheng, Wei
Wang, Huijun
Ma, Xiaojing
Qian, Yanyan
Zhang, Ping
Wu, Yao
Zheng, Fengyun
Chen, Long
Huang, Guoying
Ma, Duan
author_sort Sheng, Wei
collection PubMed
description BACKGROUND: Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and play an important role in maintaining genomic stability and gene expression. To derive insight into the association between genome-wide methylation status and tetralogy of fallot (TOF), we compared the methylation status of LINE-1 element between TOF patients and controls. The methylation of the NKX 2–5, HAND 1, and TBX 20 promoter regions was also evaluated. METHODS: Genomic DNA from right ventricular tissue samples was obtained from 32 patients with TOF and 15 control subjects. Sequenom MassARRAY platform was performed to examine the methylation levels of LINE-1, NKX2-5, HAND1 and TBX20. Mann–Whitney U test was used to compare differences in methylation levels between two groups. RESULTS: The methylation level of LINE-1 was significantly lower in patients with TOF, with a median of 57.95% (interquartile range [IQR]: 56.10%–60.04%), as opposed to 59.70% in controls (IQR: 59.00%–61.30%; P = 0.0021). The highest LINE-1 methylation level was 61.3%. The risk of TOF increased in subjects with the lowest methylation levels (less than or equal to 59.0%; OR = 14.7, 95% CI: 1.8–117.7, P = 0.014) and in those with medium methylation levels (59.0%–61.3%; OR = 2.0, 95% CI: 0.3–14.2, P = 0.65). An ROC curve analysis showed a relatively high accuracy of using the LINE-1 methylation level in predicting the presence of TOF (AUC = 0.78, 95% CI: 0.65–0.91; P = 0.002). The association of the LINE-1 methylation level with TOF was only observed in males (P = 0.006) and not in females (P = 0.25). Neither age nor gender was found to be associated with the LINE-1 methylation level in patients or controls. Higher methylation levels of NKX2-5 and HAND1 and lower methylation levels of TBX20 were also observed in patients with TOF than in controls. No association was found between the methylation levels of NKX2-5, HAND1 and TBX 20 with the LINE-1 methylation level. CONCLUSIONS: Lower LINE-1 methylation levels are associated with increased risk of TOF and may provide important clues for the development of TOF.
format Online
Article
Text
id pubmed-3408368
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-34083682012-07-31 LINE-1 methylation status and its association with tetralogy of fallot in infants Sheng, Wei Wang, Huijun Ma, Xiaojing Qian, Yanyan Zhang, Ping Wu, Yao Zheng, Fengyun Chen, Long Huang, Guoying Ma, Duan BMC Med Genomics Research Article BACKGROUND: Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and play an important role in maintaining genomic stability and gene expression. To derive insight into the association between genome-wide methylation status and tetralogy of fallot (TOF), we compared the methylation status of LINE-1 element between TOF patients and controls. The methylation of the NKX 2–5, HAND 1, and TBX 20 promoter regions was also evaluated. METHODS: Genomic DNA from right ventricular tissue samples was obtained from 32 patients with TOF and 15 control subjects. Sequenom MassARRAY platform was performed to examine the methylation levels of LINE-1, NKX2-5, HAND1 and TBX20. Mann–Whitney U test was used to compare differences in methylation levels between two groups. RESULTS: The methylation level of LINE-1 was significantly lower in patients with TOF, with a median of 57.95% (interquartile range [IQR]: 56.10%–60.04%), as opposed to 59.70% in controls (IQR: 59.00%–61.30%; P = 0.0021). The highest LINE-1 methylation level was 61.3%. The risk of TOF increased in subjects with the lowest methylation levels (less than or equal to 59.0%; OR = 14.7, 95% CI: 1.8–117.7, P = 0.014) and in those with medium methylation levels (59.0%–61.3%; OR = 2.0, 95% CI: 0.3–14.2, P = 0.65). An ROC curve analysis showed a relatively high accuracy of using the LINE-1 methylation level in predicting the presence of TOF (AUC = 0.78, 95% CI: 0.65–0.91; P = 0.002). The association of the LINE-1 methylation level with TOF was only observed in males (P = 0.006) and not in females (P = 0.25). Neither age nor gender was found to be associated with the LINE-1 methylation level in patients or controls. Higher methylation levels of NKX2-5 and HAND1 and lower methylation levels of TBX20 were also observed in patients with TOF than in controls. No association was found between the methylation levels of NKX2-5, HAND1 and TBX 20 with the LINE-1 methylation level. CONCLUSIONS: Lower LINE-1 methylation levels are associated with increased risk of TOF and may provide important clues for the development of TOF. BioMed Central 2012-06-06 /pmc/articles/PMC3408368/ /pubmed/22672592 http://dx.doi.org/10.1186/1755-8794-5-20 Text en Copyright ©2012 Sheng et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Sheng, Wei
Wang, Huijun
Ma, Xiaojing
Qian, Yanyan
Zhang, Ping
Wu, Yao
Zheng, Fengyun
Chen, Long
Huang, Guoying
Ma, Duan
LINE-1 methylation status and its association with tetralogy of fallot in infants
title LINE-1 methylation status and its association with tetralogy of fallot in infants
title_full LINE-1 methylation status and its association with tetralogy of fallot in infants
title_fullStr LINE-1 methylation status and its association with tetralogy of fallot in infants
title_full_unstemmed LINE-1 methylation status and its association with tetralogy of fallot in infants
title_short LINE-1 methylation status and its association with tetralogy of fallot in infants
title_sort line-1 methylation status and its association with tetralogy of fallot in infants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408368/
https://www.ncbi.nlm.nih.gov/pubmed/22672592
http://dx.doi.org/10.1186/1755-8794-5-20
work_keys_str_mv AT shengwei line1methylationstatusanditsassociationwithtetralogyoffallotininfants
AT wanghuijun line1methylationstatusanditsassociationwithtetralogyoffallotininfants
AT maxiaojing line1methylationstatusanditsassociationwithtetralogyoffallotininfants
AT qianyanyan line1methylationstatusanditsassociationwithtetralogyoffallotininfants
AT zhangping line1methylationstatusanditsassociationwithtetralogyoffallotininfants
AT wuyao line1methylationstatusanditsassociationwithtetralogyoffallotininfants
AT zhengfengyun line1methylationstatusanditsassociationwithtetralogyoffallotininfants
AT chenlong line1methylationstatusanditsassociationwithtetralogyoffallotininfants
AT huangguoying line1methylationstatusanditsassociationwithtetralogyoffallotininfants
AT maduan line1methylationstatusanditsassociationwithtetralogyoffallotininfants