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European Heart Journal 1999 20(21):1587-1591; doi:10.1053/euhj.1999.1696
Copyright © 1999 by the European Society of Cardiology.
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Identification of a genetic risk factor for idiopathic dilated cardiomyopathy. Involvement of a polymorphism in the endothelin receptor type A gene

Ph Charrona,b, F Tessona, O Poirierc, V Nicaudd, M Peuchmaurda, L Tiretd, F Cambienc, P Amouyele, O Dubourgf, J.-B Bouhourg, A Millaireh, Y Juillierei, P Bareissj, X André-Fouëtk, F Pouillartl, D Arveilere, J Ferrièrese, R Dorentm, G Roizèsn, K Schwartzo, M Desnosp and M Komajdaa,b,f1

a Centre de Recherche de l'Association Claude Bernard and Université Paris VI (UPRES EA no 2390)
b Service de Cardiologie
m Service de Chirurgie Cardiaque
o INSERM U153, Hôpital Pitié-Salpêtrière, Paris
c INSERM SC7, Hôpital Broussais, Paris
d INSERM U258, Hôpital Broussais, Paris
e MONICA project-France
n INSERM U249, Montpellier, Services de Cardiologie and/or Chirurgie Cardiaque
f Hôpital Ambroise Paré, Boulogne
g Hôpital Laennec, Nantes
h Hôpital Cardiologique, Lille
i Hôpitaux de Brabois, Nancy
j Hôpital Haute-Pierre, Strasbourg
k Hôpital Louis Pradel, Lyon
l Hôpital Henri Mondor, Creteil
p Hôpital Boucicaut, Paris, France

revised May 7, 1999; accepted May 12, 1999

Abstract

Background Idiopathic dilated cardiomyopathy is a frequent cause of heart failure, a major concern of public health. Although idiopathic dilated cardiomyopathy may be familial, most cases are sporadic and the disease is considered to be multifactorial, for which genetic factors may account for a significant part.

Methods and Results We hypothesized that genetic abnormalities of the endothelin pathway may be involved in idiopathic dilated cardiomyopathy pathophysiology and therefore examined the possible association between idiopathic dilated cardiomyopathy and polymorphisms in genes encoding endothelin 1, endothelin type A and type B receptors, in a case-control study (433 patients and 400 age- and sex-matched control subjects). Analysis of the Exon 8 C/T polymorphism in the endothelin receptor type A gene indicated that individuals who are homozygote for the T allele were at significantly increased risk for the disease (odds ratio: 1·9; 95% confidence interval: 1·2 to 3·01;P<0·006). Analysis of the other polymorphisms indicated that no significant difference was observed in genotype or allele frequencies between cases and controls.

Conclusions The variant in the Exon 8 of the endothelin receptor type A gene appears as a genetic risk factor for idiopathic forms of heart failure. These results provide a new approach to the pathophysiology of idiopathic dilated cardiomyopathy.

Key Words: Gene, polymorphism, heart failure, cardiomyopathy, endothelin

f1 Correspondence: Michel Komajda, MD, Centre de Recherche de l'Association Claude Bernard, Pavillon Rambuteau, Hôpital Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75651 Paris cedex 13, France.


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