Heme oxygenase-1 gene promotor microsatellite polymorphism is associated with angiographic restenosis after coronary stenting

Aims: Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation, leading to the generation of free iron, biliverdin, and carbon monoxide (CO). CO exerts potent antiproliferative and anti-inflammatory effects in the vascular walls, thereby influencing neointimal formation after vascular injury. A dinucleotide GT repeat in the promotor region of human HO-1 gene shows a length polymorphism that modulates the level of gene transcription. This study aimed to assess the association of the length of (GT)n repeats in HO-1 gene promotor with restenosis and adverse cardiac events after coronary stenting. Methods and results: Quantitative coronary angiography was evaluated before, immediately after and 6 months after stent implantation in 323 consecutive patients with successful coronary stenting. In each patient, the allele frequency of (GT)_n repeats in HO-1 gene promotor was examined. Compared with those with shorter (S, <26) GT repeats, patients with longer (L, ≥26) GT repeats on either allete had more frequent angiographic restenosis with an adjusted odds ratio (OR) of 3.74 (95% confidence interval, 1.61 to 8.70, P=0.002). Such association was even more prominant in patients with small coronary arteries or complex lesions before stenting. Besides, carriers of L/L genotype had an increased risk (adjusted OR, 3.26; 95% confidence interval, 1.58 to 6.72, P=0.001) for adverse cardiac events during follow-up. Conclusions: The length polymorphism of GT repeat in HO-1 gene promoter is an independent risk factor for angiographic restenosis as well as adverse cardiac events after coronary stenting. These findings suggest the genetic contribution to stent restenosis and support the notion that the long dinucleotide GT repeat in promotor region may interfere with HO-1 gene transcription, leading to decreased vascular protection upon injury.