Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jan 17;37(1):BSR20160408.
doi: 10.1042/BSR20160408. Print 2017 Feb 28.

Hypermethylation of brain natriuretic peptide gene is associated with the risk of rheumatic heart disease

Ni Li  1 , Dawei Zheng  1 , Lebo Sun  1 , Huoshun Shi  1 , Xiuying Zhu  1 , Guodong Xu  1 , Qinning Wang  2 , Caimin Zhu  2 , Guofeng Shao  3
Affiliations

Hypermethylation of brain natriuretic peptide gene is associated with the risk of rheumatic heart disease

Ni Li et al. Biosci Rep. .

Abstract

To investigate the contribution of brain natriuretic peptide (BNP) promoter DNA methylation to the risk of rheumatic heart disease (RHD) and the influence of warfarin anticoagulant therapy on BNP methylation levels for RHD patients after surgery. BNP methylation levels were determined by bisulfite pyrosequencing from plasma samples of RHD patients compared with healthy controls. Several factors influencing the RHD patients were included like age, smoking and cholesterol levels. A fragment of five CG sites (CpG1-5) in the promoter region of BNP gene was measured. BNP gene hypermethylation was found in CpG4 and CpG5 in RHD patients compared with non-RHD controls. A significant difference was also observed between RHD patients with long-term administration of warfarin and RHD patients who had recently undergone an operation. Moreover, single CpG4 and CpG5 analysis revealed a significant increase in methylation levels in men. BNP gene body hypermethylation is associated with the risk of RHD, and also influenced by the warfarin anticoagulant therapy of RHD patients after surgery, which could represent novel and promising targets for therapeutic development.

Keywords: DNA methylation; brain natriuretic peptide; epigenetics; pyrosequencing; rheumatic heart disease.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Primer information and correlation coefficient among the five CpGs in BNP gene promoter
Figure 2
Figure 2. Methylation levels (%) of BNP-specific methylation markers at five different CGIs
(A) The methylation levels of five CpG sites on BNP gene body of one RHD sample. (B) The methylation levels of five CpG sites on BNP gene body of one control sample (*P<0.05). (C) The methylation levels of five CpG sites on BNP gene body in all RHD groups and healthy controls.
Figure 3
Figure 3. The influence of warfarin anticoagulant haemorrhage with different times on BNP DNA methylation levels (pos.1, pos.2, pos.3, pos.4 and pos.5 are five different CG sites)
(#P<0.01,*P<0.05)
Figure 4
Figure 4. Comparison of BNP methylation levels according to sex between cases and controls; (A) CpG4 and (B) CpG5
Figure 5
Figure 5. Correlation between BNP methylation and age; (A) CpG4: pos.4 and (B) CpG5: pos.5
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Guilherme L. and Kalil J. (2010) Rheumatic fever and rheumatic heart disease: cellular mechanisms leading autoimmune reactivity and disease. J. Clin. Immunol. 30, 17–23 - PubMed
    1. Neutze J.M., (1988) Rheumatic fever and rheumatic heart disease. Report of a WHO Study Group. World Health Organ. Tech. Rep. Ser. 764, 1–58 - PubMed
    1. Li N., Lian J., Zhao S., Zheng D., Yang X., Huang X. et al. (2015) Detection of differentially expressed microRNAs in rheumatic heart disease: miR-1183 and miR-1299 as potential diagnostic biomarkers. Biomed. Res. Int. 2015, 524519. - PMC - PubMed
    1. Marijon E., Mirabel M., Celermajer D.S. and Jouven X. (2012) Rheumatic heart disease. Lancet 379, 953–964 - PubMed
    1. Limdi N.A. (2012) Warfarin pharmacogenetics: challenges and opportunities for clinical translation. Front. Pharmacol. 3, 183. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources