Abstracts (poster) - Wissenschaft Online

Jürgen Geisel, Heike Schorr, Gunar H. Heine, Marion Bodis, Ulrich Hübner, Jean-Pierre
Knapp, Wolfgang Herrmann
Decreased p66Shc promoter methylation in patients and endstage
renal disease
p66Shc is a stress response protein and partially regulated by epigenetic modifications.
Mice lacking p66Shc have reduced atherosclerosis and a prolonged life time. The aim of
the present study is to compare promoter methylation of the p66Shc gene between
healthy controls and patients with end-stage renal disease (ESRD). There are two
reasons for studying patients with ESRD. First, patients with ESRD have a disturbed
homocysteine metabolism and second an increased risk for cardiovascular disease.
In our study we measured fasting levels of homocysteine, S-adenosylmethionine (SAM),
S-adenosylhomocysteine (SAH) and 8-isoprostane in 22 patients and in 26 healthy, age-
and sex-matched controls. The methylation of the p66Shc promoter and Line-1, as
marker of whole genome methylation was quantified in peripheral blood mononuclear
cells.
In comparison to the control group homocysteine, SAM, SAH, 8-isoprostane and whole
genome methylation were significantly elevated in ESRD patients, while the p66Shc
promoter methylation was significantly reduced. A significant correlation was found
between SAH and p66Shc promoter methylation in the patient group. This observation
underlines the role of SAH as a potent inhibitor of methyltransferases. Using backward
regression analysis, we demonstrated that 8-isoprostane has a significant influence on
p66Shc promoter methylation. In the control group and in patients with ESRD increasing
8-isoprostane levels were linked to an elevated promoter methylation.
Under physiological conditions, based on the results of the control group, the p66Shc
expression is more silenced through epigenetic modifications. The atheroclerotic risk is
dramatically increased in ESRD patients; therefore our experimental results of
methylation are in accordance with the clinical situation.
Literature
1)Migliaccio E, Giorgio M, Pelicci PG. Apoptosis and aging: Role of p66Shc redox protein.
Antioxid. Redox Signal. 2006; 8:600-8.
2)Geisel J, Schorr H, Heine GH, Bodis M, Hübner U, Knapp JP, Herrmann W. Decreased
p66Shc promoter methylation in patients and end-stage renal disease. Clin. Chem. Lab.
Med. 2007;45:1764-70
contact:
Prof. Dr. Jürgen Geisel
University of Saarland
Department of Clinical Chemistry
kchjgei@uniklinikum-saarland.de
Kirrbergerstr
66421 Homburg (Germany)