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

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.

BMPR2 promoter methylation and its expression in valvular heart disease complicated with pulmonary artery hypertension

“…Anticoagulation is a key treatment for patients with VHD after valve replacement. Interestingly, long-term anticoagulation therapy with warfarin can influence DNA methylation of the BNP gene in RHD patients undergoing mechanical heart valve replacement therapy reported in our previous studies [ 16 , 25 , 26 ].…”

“…In recent years, great efforts have been made to determine whether dysregulation of DNA methylation plays an important role in the occurrence and development of VHD. In our previous study, we found DNA methylation level of the brain natriuretic peptide ( BNP ) gene was associated with pathogenesis of rheumatic heart disease (RHD) which can also cause VHD [ 15 , 16 ]. In this study, we tested BMPR2 in the VHD-PAH patients as a new biomarker since it was reported that mutations in BMPR2 cause PAH in the literature [ 17 – 19 ].…”

Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease

“…Among the evidence suggesting that the secretion of NPs is under programming since early stages is the finding of epigenetic modifications in the patterns of NPs secretion between the right and left ventricles and of other proteins that determine the difference in the force of contraction that ventricles exert [ 43 ]. There is also hypermethylation of the BNP gene in the heart of subjects with rheumatic diseases [ 134 ]. There is also a re-activation of specific heart genes including the ANP and BNP genes at the beginning of the development of heart failure [ 135 ].…”

How to design non-essential amino acid-based diet for rheumatic heart disease patients

“…Reported risk factors for rheumatic heart disease include bone morphogenetic protein receptor type II, glucokinase, interleukin 10 and brain natriuretic peptide. 1,2 These proteins possess over 5% certain amino acids with potent hydrogen bonding, including asparagine, glutamine, serine, proline, threonine, et cetera. This feature enables hydrogen bonding of amino acid residues with water and protons as well as other substances.…”