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

Q: What are the key findings of this study?

BNP gene promoter DNA methylation at CpG4 and CpG5 was significantly higher in rheumatic heart disease patients than in healthy controls (P < 0.05) and increased after 3 years of warfarin therapy.

Q: What is the clinical evidence from this study?

Study design: Case-Control. Population: Rheumatic heart disease (RHD) (n=100). Intervention: BNP gene promoter DNA methylation and warfarin anticoagulant therapy vs. Healthy non-RHD controls (and 1-month vs 3-year warfarin duration). Primary outcome: BNP gene promoter DNA methylation levels at CpG4 and CpG5 (p=<0.05).

Q: What does this research mean for the field?

Hypermethylation of the BNP gene promoter at CpG4 and CpG5 is associated with an increased risk of rheumatic heart disease and is elevated following long-term warfarin anticoagulant therapy. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To examine the contribution of brain natriuretic peptide (BNP) promoter DNA methylation to the risk of rheumatic heart disease (RHD) and assess how postoperative warfarin anticoagulation influences methylation levels.

Ni Li; Dawei Zheng; Lebo Sun; Huoshun Shi; Xiuying Zhu; Guodong Xu; Qinning Wang; Caimin Zhu; Guofeng Shao

doi:10.1042/bsr20160408

December 6, 2016Bioscience ReportsOpen Access

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

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Key result

Rheumatic heart disease is linked to higher BNP promoter methylation, which further increases with long-term warfarin.

P<0.05
n=100

Figures

Why the study?

Is BNP gene hypermethylation associated with rheumatic heart disease and influenced by warfarin therapy?

Key Points

To examine the contribution of brain natriuretic peptide (BNP) promoter DNA methylation to the risk of rheumatic heart disease (RHD) and assess how postoperative warfarin anticoagulation influences methylation levels.
Measured DNA methylation across five CG sites (CpG1–5) in the BNP gene promoter using bisulfite pyrosequencing of plasma samples from RHD patients and healthy controls.
Evaluated differences according to sex (n=35 men, n=35 women), age, lipid profiles, and duration of postoperative warfarin anticoagulation (1 month vs. 3 years).
BNP DNA methylation was significantly higher in RHD patients compared with non-RHD controls, particularly at CpG4 and CpG5.
Longer duration of warfarin therapy altered methylation patterns, with higher CpG4 and CpG5 methylation detected at 3 years compared with 1 month, alongside significant differences between 1-month users and controls at CpG2 (P=0.0033) and CpG3 (P=0.0045), and at CpG1 at 3 years (P=0.0335).
Single-site analysis revealed a significant increase in CpG4 and CpG5 methylation in men versus controls, whereas differences in women were not significant.

Study Design

Type

Case-Control (n=100)

Multicenter

No

Structured PICO

Is BNP gene hypermethylation associated with rheumatic heart disease and influenced by warfarin therapy?

P

Population

70 patients with rheumatic heart disease (50% female, mean age ~55 years) scheduled for mitral valve replacement with LVEF >50% and LVEDD <55 mm, compared with 30 age- and sex-matched healthy controls.

E

Exposure

Long-term administration of warfarin (in a subset of post-surgical RHD patients)

C

Comparator

Non-RHD healthy controls; RHD patients who recently underwent an operation

O

Outcome

BNP promoter DNA methylation levels (CpG1-5)surrogate

Main Result

p-value: p=<0.05

Limitations

Relatively limited sample size
Only a fragment of the CpG island was selected to represent the whole promoter of BNP
Possibility of unknown confounding factors such as other drug effects
Did not explore the underlying mechanism explaining why BNP methylation correlated with total cholesterol, triacylglycerol, and apolipoprotein B

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Implication

BNP gene hypermethylation is associated with rheumatic heart disease and is influenced by post-surgical warfarin therapy, suggesting a potential epigenetic biomarker or therapeutic target.

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.

Discussion

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Cite This Study

Li et al. (2016) conducted a case-control in Rheumatic heart disease (RHD) (n=100). BNP gene promoter DNA methylation and warfarin anticoagulant therapy vs. Healthy non-RHD controls (and 1-month vs 3-year warfarin duration) was evaluated on BNP gene promoter DNA methylation levels at CpG4 and CpG5 (p=<0.05). BNP gene promoter DNA methylation at CpG4 and CpG5 was significantly higher in rheumatic heart disease patients than in healthy controls (P < 0.05) and increased after 3 years of warfarin therapy.

synapsesocial.com/papers/6a75a8029c92392688b241c6 https://doi.org/10.1042/bsr20160408

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

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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