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


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, > or =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 prominent 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.
Chen
Ying-Hwa
YH
Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, 201 Sec. 2 Shih-Pai Road, Taipei 112, Taiwan, ROC.
Chau
Lee-Young
LY
Lin
Ming-Wei
MW
Chen
Lung-Ching
LC
Yo
Ming-Hui
MH
Chen
Jaw-Wen
JW
Lin
Shing-Jong
SJ
D000368:Aged; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D018895:Microsatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011859:Radiography; D015607:Stents
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1