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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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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 |
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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 |
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