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2017 ; 17
(1
): 159
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DNA methylation dysregulations in rheumatic heart valve disease
#MMPMID28623907
Shen K
; Liu H
; Jing R
; Yi J
; Zhou X
BMC Cardiovasc Disord
2017[Jun]; 17
(1
): 159
PMID28623907
show ga
BACKGROUND: The epigenetic changes underlying the development of rheumatic heart
valve disease (RHVD) remain incompletely understood. Limited evidence suggests
that abnormal DNA methylation might be involved in the pathogenesis of RHVD. In
the present study, we evaluated the DNA methylation dysregulations from
myocardial tissue in RHVD patients systematically. METHODS: Right atrial
myocardial tissue obtained from rheumatic valvular patients who had undergone
valve replacements surgery (n = 73) and were compared to healthy controls
(n = 4). the promoter methylation level of Intercellular adhesion molecule-1
(ICAM-1) gene and its correlation with ICAM-1 mRNA expression level, the global
DNA methylation level and its correlation with age and mRNA expression level of
DNA methyltransferase (DNMT) genes were detected. RESULTS: The ICAM-1 mRNA
expression was increased (healthy control vs. NHYA III, 0.70 ± 0.19 vs.
4.38 ± 3.19, p = 0.011; NYHA IIvs. NHYA III, 2.60 ± 1.99 vs. 4.38 ± 3.19,
p = 0.008) and the ICAM-1 gene was hypomethylated in RHVD patients (healthy
controls vs. NYHA II, 0.120 ± 0.011 vs. 0.076 ± 0.057, p = 0.039; healthy control
vs. NHYA III, 0.120 ± 0.011 vs. 0.041 ± 0.022, p < 0.001; NYHA IIvs. NHYA III,
0.076 ± 0.057 vs. 0.041 ± 0.022, p < 0.001). Meanwhile, The ICAM-1 mRNA
expression level has negative correlation with the mean methylation level in the
promoter region of ICAM-1 gene (r = -0.459, p < 0.001). The global DNA
methylation levels was significantly increased in RHVD patients than in healthy
controls (healthy control vs. NHYA III, 0.77 ± 0.28 vs. 2.09 ± 1.20, p = 0.017;
NYHA IIvs. NHYA III, 1.57 ± 0.78 vs. 2.09 ± 1.20, p = 0.040) and had positive
correlation with age (r = 0.326, p = 0.005), especially for older age group (?
60 years). DNMT1 likely plays an essential role in the DNA dysregulations in RHVD
patients. CONCLUSIONS: Our analysis revealed that DNA methylation dysregulations
may be relevant in the pathogenesis of RHVD.
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