Influence of ScaI and natriuretic peptide (NP) clearance receptor polymorphisms of the NP System on NP concentration in chronic heart failure.
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), 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 < or =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 in mild HF, higher ANP (P <0.05) and BNP (P <0.05) were observed in CC than A allele carriers. 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 be 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.
Vassalle
Cristina
C
Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche, Pisa, Italy. cristina.vassalle@ifc.cnr.it
Andreassi
Maria Grazia
MG
Prontera
Concetta
C
Fontana
Marianna
M
Zyw
Luc
L
Passino
Claudio
C
Emdin
Michele
M
D000368:Aged; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D020097:Natriuretic Peptide, Brain / Q000235:genetics* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*
D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C