Dataset Information

Possible Association of Polymorphisms in Ubiquitin Specific Peptidase 46 Gene With Post-traumatic Stress Disorder.

ABSTRACT: Introduction: Dynamic proteolysis, through the ubiquitin-proteasome system, has an important role in DNA transcription and cell cycle, and is considered to modulate cell stress response and synaptic plasticity. We investigated whether genetic variants in the ubiquitin carboxyl-terminal hydrolase 46 (USP46) would be associated with post-traumatic stress disorder (PTSD) in people with exposure to combat trauma using a case-control candidate gene association design. Methods: Korean male veterans exposed to the Vietnam War were grouped into those with (n = 128) and without (n = 128) PTSD. Seven tagging SNPs of USP46 were selected, and single-marker and haplotype-based association analyses were performed. All analyses were adjusted for sociodemographic factors and levels of combat exposure severity and alcohol problem. Results: One single-marker (rs2244291) showed nominal evidence of association with PTSD status and with the "re-experiencing" cluster, although the association was not significant after Bonferroni correction. No significant association with the other SNPs or the haplotypes was detected. Conclusion: The present finding suggests preliminarily that genetic vulnerability regarding the ubiquitin-proteasome system may be related to fear memory processes and the development of PTSD symptoms after trauma exposure. Further studies with a larger sample size will be needed to examine the role of the ubiquitin-proteasome system including USP46 in PTSD.

SUBMITTER: Seo JH

PROVIDER: S-EPMC8385240 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveTo conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases.Methods data sourcesPotential studies were identified through PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK), PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network) up until December 2011.Study selectionPublished observational studies reporting genotype or allele frequencies of this genetic factor in PTSD cases and in non-PTSD controls were all considered eligible for inclusion in this systematic review.Data extractionTwo reviewers selected studies for possible inclusion and extracted data independently following a standardized protocol.Statistical analysisA biallelic and a triallelic meta-analysis, including the total S and S' frequencies, the dominant (S+/LL and S'+/L'L') and the recessive model (SS/L+ and S'S'/L'+), was performed with a random-effect model to calculate the pooled OR and its corresponding 95% CI. Forest plots and Cochran's Q-Statistic and I(2) index were calculated to check for heterogeneity. Subgroup analyses and meta-regression were carried out to analyze potential moderators. Publication bias and quality of reporting were also analyzed.Results13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score) influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias.ConclusionsCurrent evidence does not support a direct effect of 5-HTTLPR polymorphisms on PTSD. Further analyses of gene-environment interactions, epigenetic modulation and new studies with large samples and/or meta-analyses are required.

Project description:The molecular factors involved in the development of Post-traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network-based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD. We used microarrays to characterize both prognostic and diagnostic molecular signatures associated to PTSD risk and PTSD status compared to control subjects. Peripheral blood leukocytes gene expression was subject to transcriptional analysis for 48 service members both prior-to and following deployment to conflict zones. Half of the subjects returned with Post-traumatic Stress Disorder (PTSD), while the other half did not.

Dataset Information

Possible Association of Polymorphisms in Ubiquitin Specific Peptidase 46 Gene With Post-traumatic Stress Disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets