Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Czarny P

PROVIDER: S-EPMC6025148 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Czarny Piotr P Wigner Paulina P Strycharz Justyna J Watala Cezary C Swiderska Ewa E Synowiec Ewelina E Galecki Piotr P Talarowska Monika M Szemraj Janusz J Su Kuan-Pin KP Sliwinski Tomasz T

PeerJ 20180626

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., <i>UNG</i> g.7245G>C (rs34259), <i>SMUG1</i> c.-31A>G (rs3087404), ...[more]

PMID: 29967751

Similar Datasets

Project description:Background:Activation of the immune system might affect the severity of depressive episodes as well as response to the antidepressant treatment. The purpose of this study was to investigate whether the occurrence of variant alleles of analyzed SNPs are involved in prevalence and progression of depression. Moreover, selected genes and SNPs have not been investigated in context of the disease severity and treatment. Therefore, six polymorphisms were selected: g.41354391A>G-TGFB1 (rs1800469), g.132484229C>A-IRF (rs2070729), g.186643058A>G-PTGS2 (rs5275), g.186640617C>T-PTGS2 (rs4648308), g.70677994G>A-TGFA (rs2166975) and g.42140549G>T-IKBKB (rs5029748). Methods:A total of 360 (180 patients and 180 controls) DNA samples were genotyped using TaqMan probes. Results:We observed that A/G of the rs2166975 TGFA, A/C of rs2070729 IRF1 and G/T of rs5029748 IKBKB were associated with an increased risk of depression development while the T/T of rs5029748 IKBKB, T/T of rs4648308 PTGS2 and G/G of rs2166975 TGFA reduced this risk. We also stratified the study group according to gender and found that genotype A/G and allele G of the rs2166975 TGFA, G/T of rs5029748 IKBKB as well as C allele of rs4648308 PTGS2, homozygote A/A and allele A of rs5275 PTGS2 were associated with increased risk of depression development in men while homozygote G/G of rs5275 PTGS2 decreased this risk. Moreover, C/T of rs4648308 PTGS2 and A/G of rs5275 PTGS2 was positively correlated with the risk of the disease occurrence in women. Furthermore, a gene-gene analysis revealed a link between studied polymorphisms and depression. In addition, A/A of rs1800469 TGFB1 was associated with earlier age of onset of the disease while G/G of this SNP increased severity of the depressive episode. Interestingly, A/C of rs2070729 IRF1 and T/T of rs5029748 IKBKB may modulate the effectiveness of selective serotonin reuptake inhibitors therapy. In conclusion, studied SNPs may modulate the risk of occurrence, age of onset, severity of the disease and response to the antidepressant treatment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets