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NISCAIR ONLINE PERIODICALS REPOSITORY (NOPR) >
NISCAIR PUBLICATIONS >
Research Journals >
Indian Journal of Biochemistry and Biophysics (IJBB) >
IJBB Vol.48 [2011] >
IJBB Vol.48(5) [October 2011] >
| Title: | Methylation of adrenergic  1 receptor is a potential epigenetic mechanism controlling antihypertensive response to metoprolol |
| Authors: | Jiang, Qixia
Yuan, Hong
Xing, Xiaowei
Liu, Jingjing
Huang, Zhijun
Du, Xia |
| Keywords: | Hypertension
Metoprolol
1-Adrenergic receptor
DNA methylation
Gene |
| Issue Date: | Oct-2011 |
| Publisher: | NISCAIR-CSIR, India |
| Abstract: | Although metoprolol is used to treat hypertension,
clinical responses are variable and unpredictable. Evidence suggests that
adrenergic 1
receptor (ADRB1, designated Adrb1
in rodents) gene polymorphisms influence the level of blood pressure
response to this drug therapy, but their presence can not predict the response
of the individual patient. The question exists whether epigenetic modifications,
such as DNA methylation could cause changes in the gene’s expression that are a
determining factor in metoprolol’s efficacy. The aim of this study was to
verify whether DNA methylation could change the expression of the ADRB1 gene, and epigenetic modification
could explain why individuals with identical
ADRB1 gene polymorphisms have different antihypertensive responses to metoprolol. H9c2 rat myocardial cells in vitro were randomly divided
into 5-aza-2'-deoxycytidine (decitabine)-treated (0.5 to 10.0 μM) and
control groups. For the in
vivo experiments, 45 spontaneously hypertensive rats (SHRs) were divided
into metoprolol-treated and control groups, and after a 4-week
intervention myocardia were harvested. Genomic
methylation-sensitive PCR was used to assess the methylation status of the Adrb1 promoter after DNA extraction from
H9c2 cells and SHR myocardia. Real-time fluorescent quantitative RT-PCR was
used to determine levels of Adrb1
mRNA. In H9c2 cells, the least degree of methylation was observed
in
the 5.0 μM decitabine treated group. Prolonged
exposure of cells to 5.0 μM decitabine resulted in downregulating methylation
of the Adrb1 promoter. Increased
levels of Adrb1 mRNA of the 5.0 μM
group demonstrated that this concentration resulted in the highest expression. Accordingly, DNA methylation
resulted in the downregulation of Adrb1
transcription. In vivo, the lower
level of methylation of the Adrb1
promoter from SHR myocardial samples demonstrated a better antihypertensive
effect by metoprolol. The expression of Adrb1
mRNA in the effective group of SHRs was significantly upregulated. In conclusion, as shown in both H9c2
cells and SHRs, downregulated methylation of the Adrb1 promoter is likely to improve the antihypertensive
efficacy of metoprolol. |
| Page(s): | 301-307 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-0959 (Online); 0301-1208 (Print) |
| Source: | IJBB Vol.48(5) [October 2011]
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