Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa 34093, Istanbul, Turkey.
Eur J Obstet Gynecol Reprod Biol. 2009 Oct;146(2):160-4. doi: 10.1016/j.ejogrb.2009.06.007. Epub 2009 Jul 9.
Oxidative stress has been postulated as a major contributor to placental hypoperfusion and ischemia in pre-eclampsia (PE). Reactive oxygen species (ROS) generated during placental ischemia can cause oxidative damage to nucleic acids. Base excision repair (BER) and nucleotide excision repair (NER) are major pathways responsible for removing the oxidative DNA damage. Polymorphisms in DNA repair genes may be associated with differences in the repair efficiency of DNA damage.
In order to investigate the possible association between DNA repair genes and PE susceptibility, we analyzed genotype and allele distributions of APE1-148, XRCC1-194, XRCC1-399 and XPD-751 genes in 101 patients with PE and 107 healthy women. Differences in genotype distributions and allele frequencies in the cases and the controls were compared for statistical significance using the chi(2)-test. Haplotype frequencies were estimated using a contingency chi(2)-test. One-way ANOVA and Mann-Whitney U-test were used for the statistics of the clinical and biochemical parameters.
No significant association between PE and the variant alleles of APE1 codon 148 (OR: 0.77, 95% CI=0.51-1.15), XRCC1 codon 194 (OR: 0.64, 95% CI=0.30-1.37), XRCC1 codon 399 (OR: 1.16, 95% CI=0.78-1.74) and XPD codon 751 (OR: 1.21, 95% CI=0.81-1.80) was observed. Results of our haplotype analysis demonstrated that there is a high linkage disequilibrium (D': 1.0, r(2)=0.042) between the haplotypes of XRCC1 codon 194 and codon 399 markers.
These preliminary results suggest that the polymorphic variants of APE1-148, XRCC1-194, XRCC1-399, and XPD-751 genes are not significant risk factors for PE development.
氧化应激被认为是子痫前期（PE）胎盘灌注不足和缺血的主要原因。胎盘缺血时产生的活性氧（ROS）可导致核酸的氧化损伤。碱基切除修复（BER）和核苷酸切除修复（NER）是负责清除氧化 DNA 损伤的主要途径。DNA 修复基因的多态性可能与 DNA 损伤修复效率的差异有关。
为了研究 DNA 修复基因与 PE 易感性之间的可能关联，我们分析了 101 例 PE 患者和 107 例健康女性中 APE1-148、XRCC1-194、XRCC1-399 和 XPD-751 基因的基因型和等位基因分布。使用卡方检验比较病例组和对照组基因型分布和等位基因频率的差异。使用列联卡方检验估计单体型频率。使用单因素方差分析和曼-惠特尼 U 检验对临床和生化参数进行统计学分析。
APE1 密码子 148（OR：0.77，95%CI=0.51-1.15）、XRCC1 密码子 194（OR：0.64，95%CI=0.30-1.37）、XRCC1 密码子 399（OR：1.16，95%CI=0.78-1.74）和 XPD 密码子 751（OR：1.21，95%CI=0.81-1.80）的变异等位基因与 PE 无显著相关性。单体型分析结果表明，XRCC1 密码子 194 和密码子 399 标记之间存在高度连锁不平衡（D'：1.0，r(2)=0.042）。
这些初步结果表明，APE1-148、XRCC1-194、XRCC1-399 和 XPD-751 基因的多态性变异不是 PE 发病的显著危险因素。
