2016
Vol. 2 No. 1: 4
iMedPub Journals
ht tp://www.imedpub.com
Research Article
DOI: 10.21767/2472-1158.100012
1
© Under License of Creative Commons Attribution 3.0 License | This article is available in: hp://www.clinical-epigenecs.imedpub.com/
Journal of Clinical Epigenetics
ISSN 2472-1158
Simonetta Friso
1#
,
Francesca Pizzolo
1#
,
Silvia Udali
1
,
Patrizia Guarini
1
,
Annalisa Castagna
1
,
Letizia Consoli
1
,
Gianluca Salvagno
2
,
Elisa Tinazzi
1
,
Patrizia Pattini
1
,
Sang-Woon Choi
3,4
,
Claudio Lunardi
1
and
Oliviero Olivieri
1
1 Department of Medicine, University of
Verona, School of Medicine, Piazzale L.A.
Scuro 10, 37134 Verona, Italy
2 Department of Pathology and Diag-
noscs, University of Verona, School of
Medicine, Piazzale L.A. Scuro 10, 37134
Verona, Italy
3 Chaum Life Center, CHA University, 442
Dosan-daero, Gangnam-gu, Seoul, 135-
948, Korea
4 Tuſts University School of Nutrion Sci-
ence and Policy, 150 Harrison Ave, Bos-
ton, MA 02111, USA
Corresponding author: Simonea Friso
simonea.friso@univr.it
University of Verona, School of Medicine,
Department of Medicine, Policlinico “G.B.
Rossi”, P.le L.A. Scuro 10, 37134 Verona,
Italy.
#
These two authors equally contributed to
this work
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Citaon: Friso S, Pizzolo F, Udali S, et al.
Epigenec Regulaon of HSD11B2 Gene by
Promoter Methylaon in Glucocorcoid-
Treated Paents. J Clin Epigenet. 2016, 2:1.
Epigenec Regulaon of HSD11B2 Gene by
Promoter Methylaon in Glucocorcoid-
Treated Paents
Abstract
Background: A reduced acvity of the 11 beta-hydroxysteroid dehydrogenase
2 (11 beta-HSD2) causes hypertension by conferring aldosterone selecvity to
mineralcorcoid receptors and eventually impairing the tetrahydrocorsol-versus
tetrahydrocorsone-metabolites (THFs/THE) shule. The 11 beta-HSD2 funcon
is modulated by glucocorcoid treatment that may induce hypertension through
a mechanism mostly unknown. Promoter methylaon, one of the main epigenec
and potenally modifiable feature of DNA, regulates HSD11B2 gene expression
and relates to the development of arterial hypertension.
Objecve: To explore the mechanism by which steroid therapy influences blood
pressure we invesgated the effect of glucocorcoid-treatment on HSD11B2
promoter methylaon and THFs/THE rao, that reflects the 11 beta-HSD2 acvity.
Method: We determined urinary THFs/THE rao by gas chromatography/mass
spectrometry and HSD11B2 methylaon in promoter Region 1 and 2 using bisulfite-
pyrosequencing in DNA from peripheral blood mononuclear cells (PBMCs) of six
normotensive subjects affected by autoimmune diseases at three me points: T0)
baseline, T1) following one-month prednisone therapy (0.5-1 mg/kg daily), and
T2) at least one year aſter withdrawal.
Results: Glucocorcoid treatment was associated with the increase of HSD11B2
promoter methylaon, that was significant for Region 1 (T0 2.4%, T1 2.8%,
P=0.046), and the concomitant raise of THFs/THE rao (T0 1.29 ± 0.80, T1 4.10 ±
1.62, P=0.043). Aſter glucocorcoid-withdrawal (T2) both parameters decreased
(methylaon 1.9%; THFs/THE rao 1.09), although not significantly. A significant
posive correlaon was observed between HSD11B2 promoter methylaon and
the THFs/THE rao.
Conclusion: High-dosage prednisone therapy alters promoter methylaon
of HSD11B2 and 11beta-HSD2 acvity, influencing blood pressure: this effect
appears slightly reversible aſter glucocorcoid-withdrawal, suggesng a dynamic
epigenec regulaon of HSD11B2.
Keywords: HSD11B2; Hypertension; Corsone; Epigenecs; DNA methylaon
Abbreviaons: 11 beta-HSD2: 11 Beta-Hydroxysteroid Dehydrogenase 2;
THFs/THE: Tetrahydrocorsol/Tetrahydrocorsone; PBMCs: Peripheral Blood
Mononuclear Cells; THF: Tetrahydrocorsol; αTHF: 5α-Tetrahydrocorsol; THE:
Tetrahydrocorsone
Received: December 24, 2015; Accepted: January 22, 2016; Published: January 30,
2016