Abstracts (poster) - Wissenschaft Online

Michael Michalkiewicz, Teresa Michalkiewicz, Kyle MacGillis
Epigenetic mechanisms in hypertension
Epigenetic variations may underlie hypertension and in fact, better than variation in DNA
sequence, may explain the late onset and quantitative nature of this disease. Genomewide
DNA methylation patterns in hypertensive Dahl S (SS) and normotensive Brown
Norway (BN) rats were assessed in a high throughput manner by methylated DNA
immunoprecipitation combined with a competitive hybridization on a microarray
(NimbleGene) covering 22K promoters. More than 2K promoters were hypermethylated
in the SS kidney. The heart methylomes were less different. Gene encoding enzymes
and involved in inflammation were the mostly methylated in the hypertensive kidney
whereas the genes involved in signal transmission were the least affected. We then
zoomed in on the known hypertension QTL areas and further narrowed down
hypermethylated targets. We then selected a few candidate genes for a detailed
nucleootide specific quantitative methylation assay using pyrosequencing of bisulfite
converted DNA. Pyrosequencing revealed hypermethylation of the renin promoter (but
not a distal CpG island) in the hypertensive kidney, consistent with the reduced renin
expression in this strain. Thus, an epigenetic mechanism may underlie some forms of
hypertension. However, since the kidney is both the culprit and the victim of
hypertension, the cause-effect relationship between the epigenome and hypertension
has to be established. Support: NIH HL-082798 and AHW MCW.
contact:
Assoc Professor Michael Michalkiewicz
Medical College of Wisconsin
Department of Physiology
mmichalk@mcw.edu
8701 Watertown Plank Road
53226 Milwaukee (USA)