Gene theory-based intervention: the effect of up-regulating microsatellite polymorphism in heme oxygenase-1 gene promotor / 中国组织工程研究

ABSTRACT

BACKGROUND: Heme oxygenase-1 (HO-1) promotor region has a pair of dinucleotide(guanosine thymidine, GT) repeats with a lengthy polymorphism, also named microsatellite polymorphism. Experiments in vitro have shown that we can indirectly learn about the level of gene transcription by measuring the number of GT repeats.OBJECTIVE: To investigate if an association exists between restenosis after percutaneous coronary intervention(PCI) and microsatellite polymorphism in HO-1 gene promoter.DESIGN: A case-control study based on the observation of the patients with coronary heart disease after undergoing coronary stenting.SETTING: Wards of the department of cardiology of a university hospital.PARTICIPANTS: A total of 118 patients were admitted from April 1996 to May 2002 at the Department of Cardiology of the First Hospital of Peking University who underwent successful coronary stenting. Inclusion criteria The patients with coronary heart disease who underwent coronary stent implantation for more than 3 months now came to perform coronary angiography in follow-up. Exclusion criteria Angiography showed that the stenosis of lumen in diameter in the patients with coronary heart disease was less than 50%and the follow-up in angiography was less than three months. There were 92males and 26 females aged(62±10) years old and the informed consents were obtained. The patients were divided into two groups according to the criteria stipulated by American Heart,Lung and Blood Association in-stent restenosis(68 cases) and non-restenosis (50 cases).METHODS: DNA of the peripheral blood was isolated from the whole blood. The length of GT repeat was confirmed by PCR amplification and Spreadex Gel electrophoresis. Selected samples were sequenced with Sanger's method.MAIN OUTCOME MEASURES: Microsatellite gene frequency of HO-1promoter and its relationship with restenosis RESULTS: Patients with GT repeats <25 GT in the HO-1 gene promoter on either allele had significantly less often restenosis than patients without (47.5% vs. 68.4% ,P<0.05). After controlling some possible confound ing factorsfor coronary heart diseases, multivariate analysis indicated that still there was a significant difference between the two groups in restenosis rate(odd ratio 0. 418,95% CI 0. 197 to 0. 887,P<0.05).CONCLUSION: The present study indicated that short(GT) n repeats of HO-1 gene promoter is associated with reduced post-PCI restenosis, which suggests the genetic contribution to in-stent restenosis after stent implantation. It may have important meanings to prevent the occurrence of restenosis.