Polymorphisms of β-adrenoceptor and Natriuretic Peptide Receptor Genes Influence the Susceptibility to and the Severity of Idiopathic Dilated Cardiomyopathy in a Chinese Cohort
Received 12 August 2008; received in revised form 2 July 2009; accepted 3 August 2009. published online 27 September 2009.
Abstract
Background
This study evaluated the potential effects of β-adrenoceptor (β-AR) and natriuretic peptide receptor (NPR) gene polymorphisms on the susceptibility to and the severity of idiopathic dilated cardiomyopathy (IDCM) in a Chinese cohort.
Methods and Results
Ten polymorphisms in the coding regions of β1-AR, β2-AR, β3-AR, NPR1, and NPR2 were genotyped in 430 IDCM patients and 468 healthy subjects. Patients with IDCM were followed for 2 years. In multi-loci combined subtype analysis, the combined profile of β-AR and NPR was significantly different between IDCM patients and controls (P < .0001), mainly influenced by 2 loci β1-Ser49Gly and NPR2-C2077T, which were also associated with the severity of IDCM. In single-loci analysis, allele frequencies of β1-Gly49, NPR1-Glu939, and NPR2-T2077 were higher in patients with IDCM than in controls. Genotypes carrying NPR2-T2077 allele showed 1.94-fold independent risk for IDCM phenotype than C2077 homozygote (P < .001). Carriers of the NPR2-T2077 or β1-Gly49 variant had worse New York Heart Association functional class or echocardiographic results and elevated serum brain natriuretic peptide, experienced severe symptoms, and required intensive medications and frequent hospitalization for heart failure. Furthermore, synergistic interactions between NPR2-C2077T and β1-Ser49Gly were detected by multifactor-dimensionality reduction method.
Conclusions
This study suggests that NPR2-T2077 and β1-Gly49 polymorphisms may be genetically synergistic adverse factors for the susceptibility to or the severity of IDCM.
1Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
2Institute of Cardiovascular Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China
Reprint requests: Wei Feng Shen, MD, PhD, Department of Cardiology, Rui Jin Hospital, 197 Rui Jin Road II, Shanghai 200025, P. R. China. Tel: +86-021-64370045-610910; Fax: +86-021-64457177.
ABSTRACT