Cor Vasa 2007, 49(4):127-133 | DOI: 10.33678/cor.2007.050

Is humoral activation in heart failure affected by a genetic predisposition?

Lenka Špinarová¹, Jindřich Špinar², Anna Vašků³, Monika Pávková-Goldbergová³, Ondřej Ludka², Josef Tomandl⁴, Jiří Vítovec¹

¹ I. interní-kardioangiologická klinika, Fakultní nemocnice u sv. Anny a Lékařská fakulta Masarykovy univerzity

² Interní-kardiologická klinika, Fakultní nemocnice Brno a Lékařská fakulta Masarykovy univerzity

³ Ústav patofyziologie, Lékařská fakulta Masarykovy univerzity

⁴ Ústav biochemie, Lékařská fakulta Masarykovy univerzity, Brno, Česká republika

Aim of study:
To document an association between the plasma levels of big endothelin and endothelin-1, clinical parameters and the two most frequent polymorphisms (-3A/-4A and G8002A) of the endothelin-1-encoding gene on the one hand and the plasma levels of TNF-a, clinical parameters and the gene polymorphisms of TNF-α -308 A/G, -238 A/G, TNF-β Ncol, and 3 TACE (tumor necrosis factor-a-converting enzyme) in patients with chronic heart failure (HF).

Patients and methods:
A total of 266 patients with symptomatic HF and documented left ventricular (LV) dysfunction were included. Genotyping was performed and the plasma levels of humoral agents were determined in 224 patients with LV dysfunction and LV ejection fraction below 40%. All had symptomatic chronic HF of NYHA Class II-IV. The cause of chronic HF was coronary heart disease in 133 and dilated cardiomyopathy in 91 patients.

Results:
No association was found between the polymorphism in the endothelin gene G85002A and the plasma levels of big endothelin and endothelin (p = 0.819; p = 0.87) or between the polymorphism -3A/-4A and the plasma levels of big endothelin and endothelin (p = 0.749; p = 0.871) as well as between the relationship of the plasma levels of TNF-a and the genotypes in the four polymorphisms in the TNF-α, β, and TACE genes. Significant correlations were established between the plasma levels of endothelin-1 and big endothelin and some clinical and laboratory parameters, in particular plasma big endothelin levels on the one hand and the degree of pulmonary congestion on the other.

Conclusion:
The hypothesis is suggested that a crucial role in endothelin and TNF-α production in heart failure is not played by the patient s genetic make-up but, rather, by their hemodynamic status due to the underlying clinical disease.

Keywords: Heart failure; Genetic polymorphisms; Endothelin; TNF-α

Published: April 1, 2007  Show citation