Czarny Piotr, Kwiatkowski Dominik, Toma Monika, Kubiak Joanna, Sliwinska Agnieszka, Talarowska Monika, Szemraj Janusz, Maes Michael, Galecki Piotr, Sliwinski Tomasz
Department of Molecular Genetics, University of Lodz, 141/143 Pomorska Street, 90-236, Lodz, Poland.
Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
Mol Neurobiol. 2017 Aug;54(6):4150-4159. doi: 10.1007/s12035-016-9971-6. Epub 2016 Jun 21.
Elevated level of DNA damage was observed in patients with depression. Furthermore, single nucleotide polymorphisms (SNPs) of base excision repair (BER) genes may modulate the risk of this disease. Therefore, the aim of this study was to delineate the association between DNA damage, DNA repair, the presence of polymorphic variants of BER genes, and occurrence of depression. The study was conducted on peripheral blood mononuclear cells of 43 patients diagnosed with depression and 59 controls without mental disorders. Comet assay was used to assess endogenous (oxidative) DNA damage and efficiency of DNA damage repair (DRE). TaqMan probes were employed to genotype 12 SNPs of BER genes. Endogenous DNA damage was higher in the patients than in the controls, but none of the SNPs affected its levels. DRE was significantly higher in the controls and was modulated by BER SNPs, particularly by c.977C>G-hOGG1, c.972G>C-MUTYH, c.2285T>C-PARP1, c.580C>T-XRCC1, c.1196A>G-XRCC1, c.444T>G-APEX1, c.-468T>G-APEX1, or c.*50C>T-LIG3. Our study suggests that both oxidative stress and disorders in DNA damage repair mechanisms contribute to elevated levels of DNA lesions observed in depression. Lower DRE can be partly attributed to the presence of specific SNP variants.
在抑郁症患者中观察到DNA损伤水平升高。此外，碱基切除修复（BER）基因的单核苷酸多态性（SNP）可能会调节这种疾病的风险。因此，本研究的目的是阐明DNA损伤、DNA修复、BER基因多态性变体的存在与抑郁症发生之间的关联。该研究对43名被诊断为抑郁症的患者和59名无精神障碍的对照者的外周血单核细胞进行。采用彗星试验评估内源性（氧化）DNA损伤和DNA损伤修复（DRE）效率。使用TaqMan探针检测BER基因的12个SNP的基因型。患者的内源性DNA损伤高于对照组，但没有一个SNP影响其水平。对照组的DRE显著更高，并且受BER SNPs调节，特别是c.977C>G-hOGG1、c.972G>C-MUTYH、c.2285T>C-PARP1、c.580C>T-XRCC1、c.1196A>G-XRCC1、c.444T>G-APEX1、c.-468T>G-APEX1或c.*50C>T-LIG3。我们的研究表明，氧化应激和DNA损伤修复机制紊乱均导致抑郁症患者中观察到的DNA损伤水平升高。较低的DRE可能部分归因于特定SNP变体的存在。
