Graduate Institute of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan, ROC.
Thromb Res. 2010 Oct;126(4):319-23. doi: 10.1016/j.thromres.2010.06.021. Epub 2010 Jul 27.
8-hydroxydeoxyguanosine, the key lesion of oxidative DNA damage, contributes to the development of coronary artery disease (CAD). In humans, 8-hydroxydeoxyguanosine is repaired by the enzyme 8-oxoguanine glycosylase I (hOGG1). We investigated the association between the hOGG1 Ser(326)Cys polymorphism and the presence and the severity of CAD in a Taiwan population. Genotypes of the hOGG1 Ser(326)Cys polymorphism were determined from 1397 participants enrolled in this study (378 CAD patients and 1019 controls). CAD severity was indicated both by number of vessels affected (single-vessel disease, SVD vs. multi-vessel disease, MVD), and by individual diffuse score. Real-time polymerase chain reaction was used to determine genotype, using allele-specific TaqMan probes. We found that presence of the hOGG1 Ser(326)Cys polymorphism was associated with a significantly increased risk of CAD and multi-vessel disease when assuming a dominant model of inheritance (OR: 1.52 [95%:1.0822.133], p=0.015; OR: 2.26 [95%:1.2324.156], p=0.007). This result was confirmed by multivariate analysis, after adjustment for age, gender, body-mass index, diabetes hypertension, hypercholesterolemia and smoking (OR: 1.78 [95%:1.1272.806], p<0.005; OR: 2.44 [95%:1.2764.651], p<0.001). In the present study, hOGG1 Ser(326)Cys polymorphism is a novel genetic marker to be independently associated with the development and severity of CAD in Taiwanese population.
8-羟基脱氧鸟苷,氧化 DNA 损伤的关键病变,有助于冠心病(CAD)的发展。在人类中,8-羟基脱氧鸟苷由酶 8-氧鸟嘌呤糖苷酶 I(hOGG1)修复。我们研究了 hOGG1 Ser(326)Cys 多态性与台湾人群 CAD 的存在和严重程度之间的关系。从参与本研究的 1397 名参与者中确定了 hOGG1 Ser(326)Cys 多态性的基因型(378 例 CAD 患者和 1019 例对照)。CAD 严重程度通过受影响血管的数量(单血管疾病,SVD 与多血管疾病,MVD)和个体弥漫评分来表示。使用等位基因特异性 TaqMan 探针的实时聚合酶链反应用于确定基因型。我们发现,在假定显性遗传模式的情况下,hOGG1 Ser(326)Cys 多态性的存在与 CAD 和多血管疾病的风险显著增加相关(OR:1.52 [95%:1.0822.133],p=0.015;OR:2.26 [95%:1.2324.156],p=0.007)。在调整年龄、性别、体重指数、糖尿病、高血压、高胆固醇血症和吸烟后,该结果通过多元分析得到证实(OR:1.78 [95%:1.1272.806],p<0.005;OR:2.44 [95%:1.2764.651],p<0.001)。在本研究中,hOGG1 Ser(326)Cys 多态性是一个新的遗传标记,可独立与台湾人群 CAD 的发生和严重程度相关。