Identification of a genetic risk factor for idiopathic dilated cardiomyopathy - Involvement of a polymorphism in the endothelin receptor type A gene

Background Idiopathic dilated cardiomyopathy is a frequent cause of heart f ailure, a major concern of public health. Although idiopathic dilated cardi omyopathy may be familial, most cases are sporadic and the disease is consi dered to be multifactorial, for which genetic factors may account for a sig nificant part. Methods and Results We hypothesized that genetic abnormalities of the endot helin pathway may be involved in idiopathic dilated cardiomyopathy pathophy siology and therefore examined the possible association between idiopathic dilated cardiomyopathy and polymorphisms in genes encoding endothelin 1, en dothelin 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 individ uals who are homozygote for the T allele were at significantly increased ri sk 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 an d controls. Conclusions The variant in the Exon 8 of the endothelin receptor type A gen e appears as a genetic risk factor for idiopathic forms of heart failure. T hese results provide a new approach to the pathophysiology of idiopathic di lated cardiomyopathy. (C) 1999 The European Society of Cardiology.