title: 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.
authors.affiliation: Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Li
authors.affiliation: Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
authors.forename: Lebo
authors.initials: L
authors.lastname: Sun
authors.affiliation: Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
authors.forename: Huoshun
authors.initials: H
authors.lastname: Shi
authors.affiliation: Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Xu
authors.affiliation: Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
authors.forename: Qinning
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Ningbo University School of Medicine, Ningbo, Zhejiang 315211, China.
authors.forename: Caimin
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Ningbo Medical Center Lihuili Hospital, Ningbo University School of Medicine, Ningbo, Zhejiang 315041, China sgf1958@sina.com.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Shao
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012214:Rheumatic Heart Disease / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D020097:Natriuretic Peptide, Brain; D014859:Warfarin; D002784:Cholesterol
keywords: DNA methylation; brain natriuretic peptide; epigenetics; pyrosequencing; rheumatic heart disease