Influence of endothelial NO synthase gene polymorphisms on development and prognosis of chronic heart failure

Abstract

Aim. To study the effects of eNOS gene polymorphisms (Glu298Asp and VNTR intron 4) on endothelial dysfunction (ED) development, chronic heart failure (CHF) severity and progression in patients with coronary heart disease (CHD) and arterial hypertension (AH).Material and methods. In total, 165 CHF patients were examined (121 men, 44 women; mean age 56,7±5,3 years). Vasomotor endothelial function was evaluated by ultrasound method in reactive hyperemia and nitroglycerin tests. Genotypes were identified by polymerase chain reaction-restriction fragment-length polymorphism analysis. The control group consisted of 114 persons (54 men, 60 women; mean age 53,2±4,9 years).Results. Glu/Glu genotype of Glu298Asp polymorphic loci was identified in CHF patients significantly more often than in controls (p<0,05), and Glu/Asp genotype was significantly more prevalent in controls (p<0,01). Glu/ Glu genotype prevalence in patients with Functional Class (FC) I (NYHA) was significantly lower than in those with FC II or FC III-IV (p<0,05). Moreover, Glu/Glu genotype was more prevalent in patients with unfavourable CHF clinical course than in those with more favourable CHF course (75,7% and 43,2%, respectively; p<0,05). This genotype was also more prevalent in patients with left ventricular ejection fraction <50%, but the difference was not statistically significant. Flow-induced dilatation of brachial artery was significantly lower in patients with Glu/Glu genotype than in those with Asp298 allele (р<0,01). Distribution of alleles and genotypes of another eNOS gene polymorphism (VNTR intron 4) was similar in CHF patients and controls.Conclusion. Alleles of eNOS gene Glu298Asp polymorphism were associated with CHF development risk and CHF clinical course features, as well as with vasomotor ED development.

Keywords

• chronic heart failure
• gene polymorphism
• enos
• endothelial dysfunction