Cor Vasa 2009, 51(3):202-209 | DOI: 10.33678/cor.2009.046

Oxide synthase donor gene polymorphisms and cardiac graft coronary artery disease

Miroslav Kocík^1,2,*, Jaroslav Hubáček³, Ivan Málek², Bronislav Janek², Michael Želízko², Antonij Slavčev⁴, Libor Kolesár⁴, Věra Lánská⁵, Jan Pirk⁶

¹ 4. interní klinika, Všeobecná fakultní nemocnice a 1. lékařská fakulty Univerzity Karlovy

² Klinika kardiologie

³ Centrum experimentální medicíny

⁴ Oddělení imunologie

⁵ Oddělení statistiky

⁶ Klinika kardiovaskulární chirurgie, Institut klinické a experimentální medicíny, Praha, Česká republika

Introduction: Cardiac graft coronary artery disease (CGCAD) constitutes of the most serious complications of heart transplantation (HTx). The principal pathophysiological trigger in the development of CGCAD is believed to be endothelial dysfunction due to a number of immunological and non-immunological factors. The key role in the regulation of a variety of processes at the level of the vessel wall is played by nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS). eNOS gene polymorphisms, affecting the availability and activity of this enzyme, may modulate NO availability at the level of the vessel wall and, given the significant protective properties of NO, also the susceptibility of the coronary arteries of the cardiac graft to develop CGCAD.

Aim: The aim of the study was to assess the effect of eNOS gene polymorphisms (intron 4, T786C, G894T) on the development of morphological traits and occurrence of clinical presentations (incidence of acute coronary syndrome, malignant arrhythmias, sudden death, heart failure after exclusion of other causes) of CGCAD in HTx recipients.
Study population and methods: The study population was made up by HTx recipients having intravascular ultrasound of the cardiac graft coronary vessels early and at 1 year post-HTx. At the same time, matched donors had eNOS genotyping in the above regions.

Results: A significant correlation was found between the 4b allele and 4b4b genotype (intron 4) on the one hand and the incidence of morphological traits of CGCAD, detected both early and at 1 year post-HTx on the other. The 4b allele and the 4b4b genotype were identified as independent risk factors for the presence of morphological traits of CGCAD early post-HTx. A significant correlation was also demonstrated between the C allele and the CC genotype (T786C) on the one hand, and the incidence of clinical presentations of CGCAD on the other.

Conclusion: A correlation was found between the eNOS gene polymorphism in the region of intron 4 and the presence of morphological traits of CGCAD both early and at 1 year post-HTx. The 4b4b genotype and the 4b allele of the eNOS gene polymorphism were identified as risk factors for the presence of morphological traits of CGCAD detected early. Likewise, a correlation was found between the eNOS T785C gene polymorphism and the incidence of clinical presentations of CGCAD.

Keywords: Heart transplantation; Coronary artery disease; Gene polymorphisms; Nitric oxide synthase

Published: March 1, 2009  Show citation