Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Int J Mol Sci. 2014 Jan 22;15(1):1671-82. doi: 10.3390/ijms15011671.
Oxidative stress (OS) is related to vascular inflammation possibly, contributing to the development of coronary ectasia (CE). Base excision repair (BER) and nucleotide excision repair are the main DNA repair pathways that can help to remove 8-hydroxydeoxyguanine (8-OHdG), a marker of OS. Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is a key enzyme of the BER pathway and catalyzes the removal of 8-OHdG. The aim of our study was to investigate the association between hOGG1 Ser326Cys gene polymorphism and CE in a Chinese population. Five-hundred forty-seven patients who underwent diagnostic coronary angiography in a tertiary medical center were recruited. The angiographic definition of CE is the diameter of the ectatic segment being more than 1.5 times larger compared with an adjacent healthy reference segment. The gene polymorphisms were analyzed by polymerase chain reaction. The urine 8OHdG concentration was measured using a commercial ELISA kit. The distribution of hOGG1 Ser326Cys genotypes was significantly different between CE and non-CE groups (p = 0.033). The odds ratio of CE development for the Ser to the Cys variant was 1.55 (95% confidence interval (CI), 1.04-2.31, p = 0.033). Both univariate and logistic regression analysis showed a significant association of hOGG1 Ser326Cys polymorphism in the dominant model with CE development (p = 0.009 and 0.011, respectively). Urine 8-OHdG levels were significantly higher in subjects carrying the hOGG1 Ser variant than in those with the Cys/Cys genotype (p < 0.03). In conclusion, our study suggests that the hOGG1 Ser326Cys gene variant might play a role in susceptibility to the development of CE.
氧化应激(OS)可能与血管炎症有关,有助于冠状动脉扩张(CE)的发展。碱基切除修复(BER)和核苷酸切除修复是主要的 DNA 修复途径,可以帮助清除 8-羟基脱氧鸟嘌呤(8-OHdG),这是 OS 的标志物。人类 8-氧鸟嘌呤 DNA 糖基化酶 1(hOGG1)是 BER 途径的关键酶,催化 8-OHdG 的去除。我们的研究旨在探讨中国人群中 hOGG1 Ser326Cys 基因多态性与 CE 的关系。我们招募了在一家三级医疗中心接受诊断性冠状动脉造影的 547 例患者。CE 的血管造影定义是扩张段的直径比相邻健康参考段大 1.5 倍以上。基因多态性通过聚合酶链反应分析。尿 8OHdG 浓度采用商业 ELISA 试剂盒测定。hOGG1 Ser326Cys 基因型的分布在 CE 和非 CE 组之间有显著差异(p=0.033)。Ser 到 Cys 变体的 CE 发展的优势比为 1.55(95%置信区间(CI),1.04-2.31,p=0.033)。单变量和逻辑回归分析均显示 hOGG1 Ser326Cys 多态性在显性模型中与 CE 发展显著相关(p=0.009 和 0.011)。携带 hOGG1 Ser 变异的受试者的尿 8-OHdG 水平明显高于 Cys/Cys 基因型的受试者(p<0.03)。总之,我们的研究表明,hOGG1 Ser326Cys 基因变异可能在易感性与 CE 发展有关。