Longitudinal epigenetic variation of DNA methyltransferase genes is associated with vulnerability to post-traumatic stress disorder.
Psychol Med
; 44(15): 3165-79, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-25065861
ABSTRACT
BACKGROUND:
Epigenetic differences exist between trauma-exposed individuals with and without post-traumatic stress disorder (PTSD). It is unclear whether these epigenetic differences pre-exist, or arise following, trauma and PTSD onset.METHOD:
In pre- and post-trauma samples from a subset of Detroit Neighborhood Health Study participants, DNA methylation (DNAm) was measured at DNA methyltransferase 1 (DNMT1), DNMT3A, DNMT3B and DNMT3L. Pre-trauma DNAm differences and changes in DNAm from pre- to post-trauma were assessed between and within PTSD cases (n = 30) and age-, gender- and trauma exposure-matched controls (n = 30). Pre-trauma DNAm was tested for association with post-trauma symptom severity (PTSS) change. Potential functional consequences of DNAm differences were explored via bioinformatic search for putative transcription factor binding sites (TFBS).RESULTS:
DNMT1 DNAm increased following trauma in PTSD cases (p = 0.001), but not controls (p = 0.067). DNMT3A and DNMT3B DNAm increased following trauma in both cases (DNMT3A p = 0.009; DNMT3B p < 0.001) and controls (DNMT3A p = 0.002; DNMT3B p < 0.001). In cases only, pre-trauma DNAm was lower at a DNMT3B CpG site that overlaps with a TFBS involved in epigenetic regulation (p = 0.001); lower pre-trauma DNMT3B DNAm at this site was predictive of worsening of PTSS post-trauma (p = 0.034). Some effects were attenuated following correction for multiple hypothesis testing.CONCLUSIONS:
DNAm among trauma-exposed individuals shows both longitudinal changes and pre-existing epigenetic states that differentiate individuals who are resilient versus susceptible to PTSD. These distinctive DNAm differences within DNMT loci may contribute to genome-wide epigenetic profiles of PTSD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtornos de Estresse Pós-Traumáticos
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Metilação de DNA
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Epigênese Genética
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DNA (Citosina-5-)-Metiltransferases
Tipo de estudo:
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Psychol Med
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos