Epigenetics of tissue angiotensinogen gene in patients with endocrine hypertension

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 723-757-Renin-Angiotensin-Aldosterone System/Endocrine Hypertension
Bench to Bedside
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-744
Yoshiyu Takeda*, Masashi Demura, Takashi Yoneda, Masashi Ohe, Mitsuhiro Kometani, Fen Wang and Yuan Cheng
Kanazawa University, Kanazawa, Japan
Purpose:Patients with primary aldosteronism (PA) have a high prevalence of concurrent metabolic abnormalities. Angiotensinogen (AGT) is highly expressed in the adipose tissue. Accumulating evidence has been suggested that elevated AGT levels in the adipose tissue are associated with hypertension and metabolic syndrome. We studied the AGT gene expression in the adipose tissues of PA and compared with those of patients with Cushing’s syndrome (CS) or non-functioning adenoma (NFA). The methylation status of the promoter region of AGT in the adipose tissues was also examined in the three groups.     

Methods: Visceral adipose tissues of PA (n=5), Cushing’s syndrome ( n=5) and  non-functioning adrenal adenomas (n=5) were collected for detection of AGT mRNA levels and promoter methylation status. Bisulfite sequencing was used for the determination of methylation status. The effect of DNA methylation on AGT promoter activity was determined using luciferase assay.

Results:The AGT gene expression levels in the adipose tissues of patients with PA were significantly higher than those of CS or NFA (p<0.05). The methylation ratio of promoter region of AGT gene was correlated with the mRNA levels of AGT in the adipose tissues. In vitro study, AGT transcription activities were highly dependent on the promoter methylation status.

Conclusions:Elevated AGT gene expression in the adipose tissues may contribute to the pathogenesis of the metabolic abnormalities in patients with PA. Epigenetic effects of aldosterone on AGT gene should be further clarified.

Nothing to Disclose: YT, MD, TY, MO, MK, FW, YC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm