Single-nucleotide polymorphisms of uracil-processing genes affect the occurrence and the onset of recurrent depressive disorder

PeerJ

Piotr Galecki¹  Monika Talarowska¹  Cezary Watala²  Justyna Strycharz³  Janusz Szemraj³  Ewa Swiderska³  Piotr Czarny³  Kuan-Pin Su⁴  Ewelina Synowiec⁵  Tomasz Sliwinski⁵  Paulina Wigner⁵ 

[1] Department of Adult Psychiatry, Medical University of Lodz, Lodz, Poland;Department of Haemostatic Disorders, Medical University of Lodz, Lodz, Poland;Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland;Department of Psychiatry and Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan;Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland;

关键词: Oxidative stress;    Depression;    DNA repair;    Uracil metabolism;    Gene polymorphism;   

DOI  :  10.7717/peerj.5116

来源: DOAJ

【 摘 要 】

Depressive disorders (DD) are known to be associated with increased DNA damage, the impairment of DNA damage repair, and the presence of single-nucleotide polymorphisms (SNPs) in DNA damage repair genes. Some indirect evidence also suggests that uracil metabolism may be disrupted in depressed patients. Therefore, the current study genotypes three SNPs localized in genes encoding uracil-processing proteins: two glycosylases, i.e., UNG g.7245G>C (rs34259), SMUG1 c.-31A>G (rs3087404), and dUTPase, i.e., DUT g.48638795G>T (rs4775748). The polymorphisms were analyzed in 585 DNA samples (282 cases and 303 controls) using TaqMan probes. The G/G genotype and G allele of UNG polymorphism decreased the risk of depression, while the G/C genotype and C allele of the same SNP increased it. It was also found that G/G carriers had their first episode significantly later than the heterozygotes. Although there was no association between the occurrence of depression and the SMUG1 SNP, a significant difference was found between the homozygotes regarding the onset of DD. In conclusion, the SNPs localized in the uracil-processing genes may modulate the occurrence and the onset of depression, which further supports the hypothesis that impairment of DNA damage repair, especially base-excision repair, may play an important role in the pathogenesis of the disease.

【 授权许可】

Unknown