Copyright © 2004 by the European Society of Cardiology.
Clinical research
Heme oxygenase-1 gene promotor microsatellite polymorphism is associated with angiographic restenosis after coronary stenting
a Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
b Institute of Clinical Medicine, National Yang-Ming University, Taipei Taiwan
c Division of Cardiovascular Research, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
d Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
e Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan
* Correspondence: Shing-Jong Lin, MD, PhD, Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital; 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan. Tel: +886-2-28757507; Fax: +886-2-28748374
E-mail address: sjlin{at}vghtpe.gov.tw
Received 13 May 2003; revised 23 September 2003; accepted 16 October 2003
Abstract
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)nrepeats 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)nrepeats 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 allele 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.
Key Words: Genes • Stents • Restenosis
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