Tarng DER-Cherng, Tsai Tzung-Jiun, Chen Wei-Ting, Liu Tsung-Yun, Wei Yau-Huei
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
J Am Soc Nephrol. 2001 Nov;12(11):2338-2347. doi: 10.1681/ASN.V12112338.
The effects of the human OGG1 gene (hOGG1) 1245C-->G polymorphism on the 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents of peripheral leukocyte DNA were investigated among chronic hemodialysis patients. First, the hOGG1 1245C-->G transversion was assessed, by using a PCR-restriction fragment length polymorphism method, among 210 hemodialysis patients and 156 healthy individuals. Second, the 8-OHdG contents in leukocyte DNA were measured, by using an HPLC-electrochemical detection method, for 112 hemodialysis patients and 112 age-, gender-, and genotype-matched healthy control subjects. The three genotypes (as dummy variables) and age, gender, dialysis duration, dialyzer membrane type, blood antioxidant levels, and iron parameters were used as independent variables and the natural logarithm of the leukocyte 8-OHdG concentration was used as a dependent variable in a forward, stepwise, multiple-regression model. The results demonstrated that the allelic frequency of hOGG1 1245G was 64.1% among 210 hemodialysis patients and 62.2% in the whole control population. The genotypic frequencies (CC/CG/GG ratio, 10%/51.9%/38.1%) for the hemodialysis patients did not differ significantly from those (16.7%/42.3%/41.0%) for the control subjects (P > 0.05, chi(2) test). The mean leukocyte 8-OHdG levels for the patients were significantly higher than those for the healthy control subjects (P < 0.001). Leukocyte 8-OHdG levels were further increased among patients with the 1245GG genotype, compared with patients with the 1245CG or CC genotype (P < 0.001, ANOVA), but levels were similar among healthy control subjects irrespective of the hOGG1 gene polymorphism. It was also observed that patients who underwent dialysis with cellulose membranes exhibited significantly higher leukocyte 8-OHdG levels than did patients who underwent dialysis with polymethylmethacrylate, polysulfone, or vitamin E-bonded membranes (P < 0.001, ANOVA). The multivariate regression analysis revealed that hOGG1 1245C-->G polymorphism and dialysis membrane type were the two independent predictors of 8-OHdG contents in leukocyte DNA from hemodialysis patients. This study demonstrated that the extent of oxidative DNA damage among chronic hemodialysis patients not only is influenced by overproduction of reactive oxygen species resulting from leukocyte contacts with complement-activating membranes and by impaired antioxidant defense mechanisms but also is genetically determined.
在慢性血液透析患者中，研究了人类OGG1基因（hOGG1）1245C→G多态性对外周血白细胞DNA中8-羟基-2'-脱氧鸟苷（8-OHdG）含量的影响。首先，采用聚合酶链反应-限制性片段长度多态性方法，对210例血液透析患者和156名健康个体进行hOGG1 1245C→G颠换评估。其次，采用高效液相色谱-电化学检测方法，对112例血液透析患者和112名年龄、性别和基因型匹配的健康对照者的白细胞DNA中的8-OHdG含量进行测定。在向前逐步多元回归模型中，将三种基因型（作为虚拟变量）以及年龄、性别、透析时间、透析器膜类型、血液抗氧化剂水平和铁参数作为自变量，将白细胞8-OHdG浓度的自然对数作为因变量。结果表明，在210例血液透析患者中，hOGG1 1245G的等位基因频率为64.1%，在整个对照人群中为62.2%。血液透析患者的基因型频率（CC/CG/GG比例为10%/51.9%/38.1%）与对照者（16.7%/42.3%/41.0%）相比，差异无统计学意义（P>0.05，卡方检验）。患者的白细胞8-OHdG平均水平显著高于健康对照者（P<0.001）。与1245CG或CC基因型患者相比，1245GG基因型患者的白细胞8-OHdG水平进一步升高（P<0.001，方差分析），但在健康对照者中，无论hOGG1基因多态性如何，其水平相似。还观察到，使用纤维素膜进行透析的患者白细胞8-OHdG水平显著高于使用聚甲基丙烯酸甲酯、聚砜或维生素E结合膜进行透析的患者（P<0.0
