Genetic Variants in Haem Oxygenase-1 and Endothelial Nitric Oxide Synthase Influence the Extent and Evolution of Coronary Artery Atherosclerosis

The genetic basis for atherosclerosis devel- opment and progression is poorly characterized. We aimed to assess the relationship between en- dothelial nitric oxide synthase (ENOS) 894 G/T, haem oxygenase-1 (HO1) dinucleotide-length pro- moter polymorphisms and coronary artery athero- sclerotic invol vement and its changes during statin therapy. Coronary angiography, intravascular ultra- sound (IVUS), IVUS-derived virtual histology (VH) and genetic polymorphism analysis were performed at study entry. Patients were randomized 1 : 1 to standard or aggressive hypolipidaemic treatment, and a follow-up evaluation was performed after twelve months. Plaque magnitude was significantly higher in carriers of HO1 risk variants when compa- red with carriers of the protective variants (< 25 GT repeats). Similarly, the total coronary atherosclerotic burden was significantly greater in HO1 risk variant carriers than in HO1 protective variant carriers. Both parameters did not differ with respect to the ENOS genotype. A higher prevalence of thin-cap fi- broatheroma (TCFA) in HO1 risk variant carriers was observed, compared with the HO1 protective variant carriers. The prevalence of TCFA was not in- fluenced by the ENOS genotype. Baseline plaque composition did not differ significantly with respect to both polymorphisms. Significant interactions be- tween plaque composition changes and ENOS and HO1 genotypes were observed during statin treat- ment. In conclusion, the protective HO1 promoter polymorphism correlates with a lower coronary ar- tery plaque burden, whereas the protective ENOS 894 G/T polymorphism seems to favourably influ- ence changes of coronary artery plaque composition during statin therapy, but has no significant correla- tion to the magnitude of coronary atherosclerosis.