Received on March 2, 2007
Accepted on August 29, 2007

Molecular Diagnostics and Genetics

Influence of ScaI and Natriuretic Peptide (NP) Clearance Receptor Polymorphisms of the NP System on NP Concentration in Chronic Heart Failure

¹ Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche, Pisa, Italy
² Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche, Pisa, Italy, and Scuola Superiore Sant'Anna, Pisa, Italy

^* To whom correspondence should be addressed. E-mail: cristina.vassalle{at}ifc.cnr.it.

Background: Genetic variants related to the natriuretic peptide (NP) system [ScaI mutated allele (A1) of the atrial NP (ANP) gene and the C variant of the natriuretic peptide clearance receptor (NPRC) gene] have been identified as independent risk factors for cardiovascular morbidity and mortality. Despite the importance of NPs in heart failure (HF), however, the role of these polymorphisms in HF has not been evaluated.

Methods: We screened 124 HF patients [mean (SD), age 66 (12) years, 100 men, ejection fraction 32% (10%), New York Heart Association (NYHA) class I–II 65, III–IV 59] for NP concentrations [ANP, brain NP (BNP) and amino-terminal pro-BNP (NT-proBNP)] and for the ScaI and NPRC variants.

Results:ScaI polymorphism had no effect on NP concentration in the NYHA I–II subgroup. Conversely, in severe HF, A1 carriers had higher ANP (P 0.05), BNP (P <0.01), and NT-proBNP (P <0.01) than A2A2 patients. After multivariate adjustment, A1 presence remained an independent predictor for increased NP. Regarding NPRC polymorphism, higher ANP (P <0.05) and BNP (P <0.05) were observed in CC than A allele carriers, in mild HF. After multivariate adjustment, however, this association did not remain significant. In severe HF, the NPRC polymorphism had no effect on NP.

Conclusions: The ScaI polymorphism of the ANP gene might represent an important additive genetic factor influencing neurohormonal activation and disease progression in severe HF. The NPRC polymorphism is not an independent determinant of NP concentration in HF.