The G-231A polymorphism in the endothelin-A receptor gene is associated with lower aortic pressure in patients with dilated cardiomyopathy.
BACKGROUND
The endothelin system (ES) plays an important role in blood pressure (BP) regulation and also in the pathophysiology of idiopathic dilated cardiomyopathy (DCM). Recently, we demonstrated that a genetic polymorphism in the endothelin A (ET(A)) receptor gene was associated with survival in DCM patients. The aim of this study was to determine whether polymorphisms in the ET(A) receptor gene might be associated with the severity of DCM.


METHODS
One hundred twenty-four consecutively recruited unrelated patients with DCM, who underwent a detailed phenotyping protocol, were genotyped for the ET(A) receptor G-231A polymorphism using a hybridization technique with allele-specific oligonucleotides.


RESULTS
The exon 1 G-231A polymorphism of the ET(A) receptor gene, upstream of the translation start site, was significantly associated with directly measured intra-aortic pressure in that -231A allele carriers had significantly lower systolic (P = .0043), as well as mean (P = .0016) and diastolic (P = .0041) aortic pressure compared to noncarriers. The association of ET(A) G-231A with aortic pressure was independent from other factors such as prior medication, left ventricular end-diastolic diameter, age, gender, and New York Heart Association (NYHA) functional classification. However, no such association was seen for cuff BP and survival rates were not significantly different between -231A allele carriers and -231G homozygotes (log rank test, P = .66). No significant association with any other parameter investigated in the present study could be observed, even when men and women were analyzed separately.


CONCLUSIONS
Our results suggest an association of genetic variation in the ET(A) receptor gene with aortic pressure in patients with DCM.
Telgmann
Ralph
R
Leibniz-Institute for Arteriosclerosis Research, Department of Molecular Genetics of Cardiovascular Disease, University of Muenster, Domagkstrasse 3, D-48149 Muenster, Germany.
Harb
Bassam A
BA
Ozcelik
Cemil
C
Perrot
Andreas
A
Schönfelder
Jacqueline
J
Nonnenmacher
Andreas
A
Brand
Marcus
M
Schmidt-Petersen
Klaus
K
Dietz
Rainer
R
Kreutz
Reinhold
R
Osterziel
Karl-Josef
KJ
Paul
Martin
M
Brand-Herrmann
Stefan-Martin
SM
D000368:Aged; D001011:Aorta / Q000503:physiopathology*; D001483:Base Sequence; D001794:Blood Pressure / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000503:physiopathology; D017023:Coronary Angiography; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044022:Receptor, Endothelin A / Q000235:genetics*
D044022:Receptor, Endothelin A