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Mitochondrial genetic variants identified to be associated with posttraumatic stress disorder.

ABSTRACT: Despite the fact that mitochondrial dysfunctions are increasingly recognized as key components in stress-related mental disorders, very little is known about the association between posttraumatic stress disorder (PTSD) and mitochondrial variants. To identify susceptibility mitochondrial genes for PTSD, we analyzed a total number of 978 mitochondrial single-nucleotide polymorphisms (mtSNPs) in a sample of 1238 individuals participating in the KORA (Cooperative Health Research in the Region of Augsburg) study. Participants were classified with 'no PTSD', 'partial PTSD' or 'full PTSD' by applying the Posttraumatic Diagnostic Scale and the Impact of Event Scale. To assess PTSD-mtSNP association while taking heteroplasmy into account, we used the raw signal intensity values measured on the microarray and applied linear regression. Significant associations were obtained between full versus no PTSD and two mtSNPs; mt8414C->T (?=-0.954±0.06, Padjusted=0.037) located in adenosine triphosphate (ATP) synthase subunit 8 (MT-ATP8) and mt12501G->A (?=-1.782±0.40, Padjusted=0.015) located in the NADH dehydrogenase subunits 5 (MT-ND5). Heteroplasmy for the two variants towards a larger number of the respective minor alleles increases the risk of having PTSD. NADH dehydrogenase and ATP synthase are both linked to the regulation of reactive oxygen species. Our results highlight the important role of the mitochondrial genome among the factors that contribute to the risk of PTSD. Mitochondrial genetic variants may be more important than has previously been assumed, leading to further insights regarding effects of existing medications, or even to the development of innovative treatments. As this is the first mitochondrial genome-wide association study for PTSDs, further analyses are needed to follow up on the present findings.

SUBMITTER: Flaquer A

PROVIDER: S-EPMC4354348 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Mitochondrial genetic variants identified to be associated with posttraumatic stress disorder.

Flaquer A A Baumbach C C Ladwig K-H KH Kriebel J J Waldenberger M M Grallert H H Baumert J J Meitinger T T Kruse J J Peters A A Emeny R R Strauch K K

Translational psychiatry 20150310

Despite the fact that mitochondrial dysfunctions are increasingly recognized as key components in stress-related mental disorders, very little is known about the association between posttraumatic stress disorder (PTSD) and mitochondrial variants. To identify susceptibility mitochondrial genes for PTSD, we analyzed a total number of 978 mitochondrial single-nucleotide polymorphisms (mtSNPs) in a sample of 1238 individuals participating in the KORA (Cooperative Health Research in the Region of Aug ...[more]

PMID: 25756807

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Project description:Posttraumatic stress disorder (PTSD) is a complex mental disorder and can severely interfere with the normal life of the affected people. Previous studies have examined the association of PTSD with genetic variants in multiple dopaminergic genes with inconsistent results. To perform a systematic literature search and conduct meta-analysis to examine whether genetic variants in the dopaminergic system is associated with PTSD. Data Sources: PubMed, Cochrane Library, Embase, Google Scholar, and HuGE. Study eligibility criteria and participants: The studies included subjects who had been screened for the presence of PTSD; the studies provided data for genetic variants of genes involved in the dopaminergic system; the outcomes of interest included diagnosis status of PTSD; and the studies were case-control studies. Study appraisal and synthesis methods: Odds ratio was used as a measure of association. We used random-effects model in all the meta-analyses. Between-study heterogeneity was assessed using I², and publication bias was evaluated using Egger test. Findings from meta-analyses were confirmed using random-effects meta-analyses under the framework of generalized linear model (GLM). A total of 19 studies met the eligibility criteria and were included in our analyses. We found that rs1800497 in DRD2 was significantly associated with PTSD (OR = 1.96, 95% CI: 1.15-3.33; P = 0.014). The 3'-UTR variable number tandem repeat (VNTR) in SLC6A3 also showed significant association with PTSD (OR = 1.62, 95% CI: 1.12-2.35; P = 0.010), but there was no association of rs4680 in COMT with PTSD (P = 0.595). Sample size is limited for some studies; type and severity of traumatic events varied across studies; we could not control for potential confounding factors, such as age at traumatic events and gender; and we could not examine gene-environment interaction due to lack of data. We found that rs1800497 in DRD2 and the VNTR in SLC6A3 showed significant association with PTSD. Future studies controlling for confounding factors, with large sample sizes and more homogeneous traumatic exposure, are needed to validate the findings from this study.

Project description:Posttraumatic stress disorder (PTSD) is a trauma and stressor related disorder that may develop after exposure to an event that involved the actual or possible threat of death, violence or serious injury. Its molecular underpinning is still not clear. Brain-derived neurotrophic factor (BDNF) modulates neuronal processes such as the response to stress, but also weight control, energy and glucose homeostasis. Plasma BDNF levels and a functional BDNF Val66Met (rs6265) polymorphism were reported to be associated with PTSD, as well as with increased body mass index (BMI) and dyslipidaemia in healthy subjects and patients with cardio-metabolic diseases, but these results are controversial. The other frequently studied BDNF polymorphism, C270T (rs56164415), has been associated with the development of different neuropsychiatric symptoms/disorders. As far as we are aware, there are no data on the association of BDNF Val66Met and C270T polymorphisms with metabolic indices in PTSD. Due to high rates of obesity and dyslipidaemia in PTSD, the aim of this study was to elucidate the association of BDNF Val66Met and C270T polymorphisms with BMI and lipid levels in veterans with PTSD. We hypothesized that BDNF variants contribute to susceptibility to metabolic disturbances in PTSD. The study included 333 Caucasian males with combat related PTSD, diagnosed according to DSM-5 criteria. Genotyping of the BDNF Val66Met and C270T polymorphisms was performed using the real-time PCR method. Results were analyzed using hierarchical multiple linear regression and the Mann-Whitney test, with p-value corrected to 0.005. The results showed that BDNF Val66Met and BDNF C270T polymorphisms were not significantly associated with BMI, total cholesterol, LDL-cholesterol, HDL-cholesterol or triglycerides. Although the BDNF C270T polymorphism was nominally associated only with HDL-cholesterol in veterans with PTSD, this significance disappeared after controlling for the effect of age. Namely, slightly higher plasma HDL values in T allele carriers, compared to CC homozygotes, were associated with differences in age. Our results, controlled for the critical covariates, revealed that BDNF Val66Met and C270T were not significantly associated with metabolic indices in veterans with PTSD and that these genetic variants do not contribute to susceptibility to metabolic disturbances in PTSD.

Dataset Information

Mitochondrial genetic variants identified to be associated with posttraumatic stress disorder.

Publications

Mitochondrial genetic variants identified to be associated with posttraumatic stress disorder.

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