eNOS基因多态性与冠状动脉支架置入后再狭窄的相关性

Association between polymorphism of 27 bp variable number of tandem repeats (VNTR) in endothelial nitric oxide synthase (eNOS) gene and restenosis after coronary stenting

目的:探讨内皮型一氧化氮合酶(eNOS)基因27bp数目可变的串联重复序列(VNTR)多态性与中国汉族人群中冠状动脉支架置入后再狭窄的相关性.方法:①收集冠状动脉支架术后冠状动脉造影随访患者105例,同时收集传统危险因素、手术相关因素信息.②应用聚合酶链反应(PCR)及琼脂糖凝胶电泳检测患者的基因型,同时进行基因测序.③硝酸还原酶法测定空腹血清一氧化氮代谢物(NOX)水平,用放射免疫法测定内皮素(ET)水平.结果:①入选的105例患者中再狭窄者65例,无再狭窄者40例;②两组人群eNOS基因27bpVNTR均存在重复4次、5次两种等位基因,以及4/4纯合、4/5杂合和5/5纯合3种VNTR基因型,但等位基因与基因型的分布频率存在差异.再狭窄组重复4次的等位基因频率和4/5杂合、4/4纯合的基因型频率明显高于非再狭窄组;③入选者中4/4纯合+4/5杂合基因型空腹血清NOX,NOX/ET明显低于5/5纯合基因型,P<0.05.结论:eNOS基因VNTR重复4次的等位基因携带者冠状动脉支架置入后再狭窄危险性较高,重复4次等位基因携带者术后再狭窄发生率高,其可能机制是eNOS功能缺失或减低进而减少内皮NO的释放,损害内皮功能,刺激血管平滑肌过度增生从而加速再狭窄的进程.

AIM: To investigate the association of the polymorphism of 27 bp variable number of tandem repeats (VNTR) in endothelial nitric oxide synthase (eNOS) gene with restenosis after coronary stenting in Chinese population. METHODS: ① One hundred and five cases who had undergone coronary stenting and coronary angiography at least 3 months after the procedure were enrolled. Clinical risk factors and procedure-related factors were collected. ② Genotypes of the 105 patients were determined by polymerase chain reaction (PCR) and agarose gel electrophoresis and gene sequenciong. ③ Fasting serum nitric oxide metabolite (NOX) and endothelin (ET) were measured by nitrate reductase and radioim munoassay respectively. RESULTS: ① In the 105 enrolled patients, 65 cases developed in-stent restenosis and the others were free from restenosis. ② Two alleles, containing 4 and 5, and three genotypes (namely 4/4-homozygous, 4/5-heterozygous and 5/5-heterozygous) were identified in both the patients with restenosis and the patients without restenosis. ③ The overall distributions of either allele or genotype frequencies differed significantly between the two groups and the genotypes of the 4 repeat alleles (4/5-heterozygous and 4/4-homozygus) were more frequent in the patients with restenosis than in those without restenosis (P<0.05). CONCLUSION: The 4 repeat alleles in eNOS gene may have a higher risk of restenosis after coronary stenting and the 4 repeat alleles in eNOS gene may lead to restenosis by reducing NO release of endothelium and damaging the endothelial function.